Hypertension - High Blood Pressure

Etiology and Classification

A. Primary (Essential) Hypertension

In about 95% of cases, no cause can be established. ( I believe everything has a cause, finding it is where the work comes in) This occurs in 10-15% of white adults and 20-30% of black adults in the USA. The onset is usually between ages 25-55 and it is uncommon before age 20. In young people, secondary hypertension resulting from renal insufficiency, renal artery stenosis, or coarctation of the aorta makes up a greater (but still relatively small) proportion of cases.

Elevations in pressure are often intermittent early in the course. Even in established cases, the blood pressure fluctuates widely in response to emotional stress and physical activity. Blood pressures taken by the patient at home or during daily activities using a portable apparatus are often lower than those recorded in the office, clinic, or hospital and may be more reliable in estimating prognosis. Patients with daytime average pressures less than 135/85 mm Hg have a low rate of cardiovascular complications and a low prevalence of left ventricular hypertrophy, suggesting that this is an appropriate ambulatory blood pressure criterion for diagnosing hypertension.

The pathogenesis of essential hypertension is multifactorial. Genetic factors play an important role. Children with one (and more so with two) hypertensive parents have higher blood pressures.( This is because families tend to have the same lifestyle and diet. If your genes predispose you to a condition, it does not mean you will get it, it only means that you have to express or activate the situation for the gene. If lifestyles and diet are changed, the gene will most likely not express the disease). Environmental factors also are significant. Increased salt intake has long been incriminated. (Not entirely true anymore). It alone is probably not sufficient to elevate blood pressure to abnormal levels; a combination of too much salt plus a genetic predisposition is required. Other factors that may be involved in the pathogenesis of essential hypertension are the following:

1. Sympathetic nervous system hyperactivity- Sympathetic nervous system hyperactivity is most apparent in younger hypertensives, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor. (Not true at all). Insensitivity of the baroreflexes may play a role in the genesis of adrenergic hyperactivity. (The sympathetic nervous system activity can be altered by biofeedback and chiropractic).

2. Renin-angiotensin system- Renin, a proteolytic enzyme, is secreted by the juxtaglomerular cells surrounding afferent arterioles in response to a number of stimuli, including reduced renal perfusion pressure, diminished intravascular volume, circulating catecholamines, increased sympathetic nervous system activity, increased arteriolar stretch, and hypokalemia. Renin act on angiotensinogen to cleave off the ten-aminoacid peptide angiotensin I. This peptide is then acted upon by angiotensin-converting enzyme to create the eight-aminoacid peptide angiotensin II, a potent vasoconstrictor and a major stimulant of aldosterone release from the adrenal glands. The incidence of hypertension and its complications may be increased in individuals with the DD genotype of the allele coding for angiotensin-converting enzyme. Despite the role of this system in the regulation of blood pressure, it probably does not play a primary role in the pathogenesis of most essential hypertension. Patients with low plasma renin activity may have higher intravascular volumes. Black hypertensives (changes here most likely show the genetics related to African vs. American types of diet. The black diet in America is appallingly bad as apposed to the high fiber ancestral diet from which they descended) and older patients tend to have lower plasma renin activity; plasma levels are classified in relation to dietary sodium intake or urinary sodium excretion. Approximately 10% of essential hypertension patients have high levels, 60% normal, and 30% low. Measure is of little clinical utility.

3. Defect in natriuresis- Normal individuals increase their renal sodium excreting in response to elevations in arterial pressure and to a sodium or volume load. Hypertensive patients, particularly when their blood pressure is normal, exhibit a diminished ability to excrete a sodium load. This defect may result in increased plasma volume and hypertension. However, during chronic hypertension, a sodium load is usually handled normally.

4. Intracellular sodium (Na+) and calcium (Ca++)- Intracellular Na+ is elevated in blood cells and other tissues in essential hypertension. This may result from abnormalities in Na+-K+ exchange and other Na+ transport mechanisms. An increase in intracellular Na+ may lead to increased intracellular Ca++ concentrations as a result of facilitated exchange and might explain the increase in vascular smooth muscle tome that is characteristic of established hypertension.

5. Exacerbating factors- A number of conditions elevate blood pressure, especially in predisposed individuals. Obesity is associated with an increase in intravascular volume and an elevated cardiac output. Weight reduction lowers blood pressure modestly. The relationship between sodium intake and hypertension remains controversial, and some - not all - hypertensives respond to high salt intake with substantial blood pressure increases. Hypertensive patients should consume no more than 100 mmol/d of salt (2.4 g of sodium, 6g of sodium chloride daily).

Excessive use of alcohol also raises blood pressure, perhaps by increasing plasma catecholamines. Hypertension can be difficult to control in patients who consume more that 40g of ethanol (two drinks) daily or drink in binges. Cigarette smoking raises blood pressure, again by increasing plasma norepinephrine.(possibly by also causing hypertrophy of vascular smooth muscle). Although the long-term effect of smoking on blood pressure is less clear, the synergistic effects of smoking and high blood pressure on cardiovascular risk are well documented. The relationship between stress and hypertension is not established. (According to whom? It is biochemically and physiologically established). Polycythemia, whether primary or due to diminished plasma volume, increases blood viscosity and may raise blood pressure. Non-steroidal anti-inflammatory agents (aspirin, Tylenol, etc.) produce increases in blood pressure averaging 5 mm Hg, and are best avoided in patients with borderline or elevated blood pressures. (Does that statement make you ask why then do doctors prescribe an aspirin a day? Find out here). Low potassium intake is associated with higher blood pressure in some patients; an intake of 90 mmol/d is recommended.

B. Secondary Hypertension

Approximately 5% of patients with hypertension have specific causes. (Everything has a cause). The history, examination, and routine laboratory tests may identify such patients. In particular, patients who develop hypertension at an early age without a positive family history, those who first exhibit hypertension when over age 50, or those previously well-controlled but who become refractory to treatment are more likely to have secondary hypertension. Causes include the following:

1. Estrogen use- A small increase in blood pressure occurs in most women taking oral contraceptives, but considerable rises are noted occasionally. This is caused by volume expansion due to increased activity of the renin-angiotensin-aldosterone system. The primary abnormality is an increase in the hepatic synthesis of renin substrate. Five percent of women taking oral contraceptives chronically will exhibit a rise in blood pressure above 140/90 mm Hg; this is twice the expected prevalence. Contraceptive-related hypertension is more common in women over 35 years of age, in those who have taken contraceptives for more than 5 years, and in obese individuals. It is less common in those taking low-dose estrogen tablets. In most, hypertension is reversible by discontinuing the contraceptive, but it may take several weeks. Postmenopausal estrogen does not cause hypertension. These agents maintain endothelium-mediated vasodilation.

2. Renal disease- Renal parenchymal disease is the most common cause of secondary hypertension. Hypertension may result from glomerular diseases, tubular interstitial disease, and polycystic kidneys. Most cases are related to increased intravascular volume or increased activity of the renin-angiotensin-aldosterone system. Hypertension accelerates progression of renal insufficiency, and rigorous control to target blood pressure of 130/85 or lower will retard this progression. Diabetic nephropathy is another cause of chronic hypertension. This process is exacerbated by intraglomerular hypertension, itself worsened by systemic hypertension. Dilation of the efferent arterioles by angiotensin-converting enzyme inhibition reduces the rate of progression.

3. Renal vascular hypertension- Renal artery stenosis is present in 1-2% of hypertensive patients. Its cause in most younger individuals is fibromuscular hyperplasia, which is most common in women under 50. The remainder of renal vascular disease is due to atherosclerotic stenoses of the proximal renal arteries. The mechanism of hypertension is excessive renin release due to reduction in renal blood flow and perfusion pressure. Renal vascular hypertension may occur when a single branch of the renal artery is stenotic, but in as many as 25% of patients both arteries are obstructed.

Renal vascular hypertension should be suspected in the following circumstances: 1) if the documented onset is below age 20 or after age 50; 2) if there are epigastric or renal artery bruits; 3) if there is atherosclerotic disease of the aorta or peripheral arteries; or 4) if there is abrupt deterioration in renal function after administration of angiotensin-converting enzyme inhibitors. Additional evaluation is indicated in such patients, especially if hypertension is difficult to control.

There is no ideal screening test for renal vascular hypertension. If the suspicion of renal vascular hypertension is sufficiently high, renal arteriography, the definitive diagnostic test, is the best approach. Where suspicion is moderate to low, radioisotope renography before and after administration of an angiotensin-converting enzyme inhibitors is one standard approach. The baseline study may show a smaller kidney with diminished function on the side of the stenosis. Post-drug (captopril or enalaprilat) uptake and clearance of the radiotracer are delayed. However, bilateral disease may be difficult to detect if both kidneys are equally affected, and this test becomes insensitive in the presence of renal insufficiency. Duplex doppler flow studies and noninvasive angiograms using CT or MRI each have proponents, but the results vary greatly between centers. Except when stenosis is critical (>80-90%) and unifocal, its significance may be assessed by measuring differences in renin activity between the renal veins. If the lesion is not associated with an increase in renin activity, hypertension often persists despite correction.

Young individuals and good-risk patients of any age who have not responded to medical therapy should have the lesion corrected. Percutaneous transluminal angioplasty or stent placement is the preferred approach for fibromuscular hyperplasia and for discrete stenotic arteriosclerotic lesions that do not involve the renal artery ostium. In older individuals with arteriosclerosis, only a minority experience complete normalization without continued drug therapy. Thus, renal function and blood pressure should be closely monitored during the first weeks of therapy in patients in whom this is a consideration.

4. Primary hyperaldosteronism and Cushing's syndrome- Patients with excess aldosterone secretion make up less than 0.5% of all cases of hypertension. The usual lesion is an adrenal adenoma, though some patients have bilateral adrenal hyperplasia. The diagnosis should be suspected when patients present with hypokalemia prior to diuretic therapy associated with excessive urinary potassium excretion and suppressed levels of plasma renin activity; serum sodium usually exceeds 140 meq/L. Aldosterone concentrations in urine and blood are elevated. The lesion can be demonstrated by CT scanning or MRI. Less commonly, patients with Cushing's syndrome (excess cortisol) may present with hypertension.

5. Pheochromocytoma- Although hypertension due to pheochromocytoma may be episodic, most patients have sustained elevations. (pheochromocytoma has intermittent hypertension, whereas neuroblastoma has constant hypertension. Neuroblastoma is the most common tumor of the adrenal medulla in children, but it can occur anywhere in the sympathetic chain). The majority of patients have orthostatic falls in blood pressure, the converse of essential hypertension; some develop glucose intolerance.

6. Coarctation of the aorta- (uncommon cause of hypertension. Usually the person is hypertensive in the arms, but has little pulse in the legs. Can be seen on X-ray as rib notching)

7. Hypertension associated with pregnancy- Hypertension occurring de novo or worsening during pregnancy is one of the commonest causes of maternal and fetal morbidity and mortality.

8. Other causes of secondary hypertension- Hypertension has also been associated with hypercalcemia due to any cause, acromegaly, hyperthyroidism, hypothyroidism, and a variety of neurologic disorders causing increased intracranial pressure. A number of medications may cause or exacerbate hypertension ( most importantly, cyclosporine and NSAIDs- aspirin).

Complications of Untreated Hypertension

Complications of hypertension are related either to sustained elevations of blood pressure, with consequent changes in the vasculature and heart, or to atherosclerosis that accompanies and is accelerated by long-standing hypertension. The excess morbidity and mortality related to hypertension are progressive over the whole range of systolic and diastolic blood pressures; the risk approximately doubles for each 6 mm Hg increase in diastolic blood pressure. However, target organ damage varies markedly between individuals with similar levels of office hypertension. Ambulatory pressures are more closely related to end organ damage.

A. Hypertensive Cardiovascular Disease

Cardiac complications are the major causes of morbidity and mortality in essential hypertension, and preventing them is a major goal of therapy. ECG evidence of left ventricular hypertrophy is found in up to 15% of chronic hypertensives. It is an indication of increased risk for morbidity and mortality; for any level of blood pressure, its presence is associated with incremental risk. ECG left ventricular hypertrophy is a powerful predictor of prognosis. Left ventricular hypertrophy may cause or facilitate many cardiac complications of hypertension, including congestive heart failure, ventricular arrhythmias, myocardial ischemia, and sudden death.

Left ventricular diastolic dysfunction, which may present with all of the signs and symptoms of congestive heart failure, is common inpatients with long-standing hypertension. The occurrence of heart failure is reduced by 50% with antihypertensive therapy. Hypertensive left ventricular hypertrophy regresses with therapy and is most closely related to the degree of systolic blood pressure reduction. Diuretics have produced equal or greater reductions of left ventricular mass when compared with other drug classes..

B. Hypertensive Cerebrovasular Disease and Dementia

Hypertension is the major predisposing cause of stroke, especially intracerebral hemorrhage but also ischemic cerebral infarction. Cerebrovascular complications are more closely correlated with the systolic than the diastolic blood pressure. The incidence of these complications is markedly reduced by antihypertensive therapy. Preceding hypertension is associated with a higher incidence of subsequent dementia, both the vascular and the Alzheimer types. Effective blood pressure control may modify the risk or rate of progression of cognitive dysfunction.

C. Hypertensive Renal Disease

Chronic hypertension leads to nephrosclerosis, a common cause of renal insufficiency; aggressive blood pressure control attenuates the process. In patients with hypertensive nephropathy, the blood pressure should be 130/85 mm Hg or lower when proteinuria is present. Secondary renal disease is more common in blacks, particularly when accompanying diabetes is present. Hypertension also plays an important role in accelerating the progression of other forms of renal disease, most commonly diabetic nephropathy. ACE inhibitors are particularly effective in preventing the latter complication, but these agents appear to prevent the progression of other forms of nephropathy.

D. Aortic Dissection

Hypertension is a contributing factor in many patients with dissection of the aorta.

E. Atherosclerotic Complications

Most Americans with hypertension die of complications of atherosclerosis, but the linkage between hypertension and atherosclerotic cardiovascular disease is much less close than that with the previously discussed complications. Effective antihypertensive therapy is thus less successful in preventing complications of coronary heart disease.

Clinical Findings

A. Symptoms

Mild to moderate essential hypertension is asymptomatic for many years. Suboccipital pulsating headaches, characteristically occurring early in the morning and subsiding during the day, are said to be characteristic, but any type of headache may occur. Accelerated hypertension is associated with somnolence, confusion, visual disturbances, and nausea and vomiting (hypertensive encephalopathy).

Patients with pheochromocytomas that secrete predominantly norepinephrine usually have sustained hypertension but may have episodic hypertension. Attacks of anxiety, palpitation, profuse perspiration, pallor, tremor, and nausea and vomiting occur; blood pressure is markedly elevated, and angina or acute pulmonary edema may occur. In primary aldosteronism, patients may have muscular weakness, polyuria, and nocturia due to hypokalemia; malignant hypertension is rare.

Chronic hypertension often leads to left ventricular hypertrophy, which may be associated with diastolic or, in late stages, systolic dysfunction. Exertional and paroxysmal nocturnal dyspnea may result. Severe left ventricular hypertrophy predisposes to myocardial ischemia (especially when concomitant coronary artery disease is present), ventricular arrhythmias, and sudden death.

Cerebral involvement causes (1) stroke due to thrombosis or (2) small or large hemorrhage from microaneurysms of small penetrating intracranial arteries. Hypertensive encephalopathy is probably caused by acute capillary congestion and exudation with cerebral edema. The findings are usually reversible if adequate treatment is given promptly. Although there is no strict correlation of diastolic blood pressure with hypertensive encephalopathy, it usually exceeds 130 mm Hg.

B. Signs

1. Blood pressure-Blood pressure should be measured after the patient has rested 10 or more minutes in familiar, quiet, warm surroundings. On the initial observation, pressure should be examined in both arms and, if lower extremity pulses are diminished, in the legs to exclude coarctation of the aorta. Supine and standing measurements should be made to detect a postural drop, usually present in pheochromocytoma. Elderly patients may have falsely elevated readings by sphygmomanometry because of noncompressible vessels. This may be suspected in the presence of Osler's sign - a palpable brachial or radial artery when the cuff is inflated above systolic pressure. Occasionally, it may be necessary to maker direct measurements of intra-arterial pressure, especially in patients with apparent severe hypertension who do not tolerate therapy.

2. Retinas-The Keith-Wagener (KW) classification of retinal changes in hypertension, in spite of deficiencies, presage a worse prognosis when stage II or higher changes are present.

3. Heart and arteries-A loud aortic second sound and an early systolic ejection click may occur. Left ventricular enlargement with a left ventricular heave indicates well-established disease. Older patients frequently have systolic ejection murmurs resulting from aortic sclerosis, and these may evolve to significant aortic stenosis in some individuals. Aortic insufficiency may be auscultated in up to 5% of patients, and hemodynamically insignificant aortic insufficiency can be detected by Doppler echocardiography in 10-20%. A presystolic (S4) gallop due to decreased compliance of the left ventricle is quite common.

4. Pulses-The timing of upper and lower extremity pulses should be compared to exclude coarctation of the aorta. All major peripheral pulses should be evaluated to exclude aortic dissection and peripheral atherosclerosis, which may be associated with renal artery involvement.

Nonpharmalogical Therapy

All patients with high normal or elevated blood pressure, those who have a family history of cardiovascular complications of hypertension, and those who have multiple coronary risk factors should be counseled about nonpharmacologic approaches to lowering blood pressure. Approaches of proved but modest value include weight reduction, reduced alcohol consumption, and in some patients reduced salt intake. Increased activity levels should be encouraged in previously sedentary patients, but strenuous exercise training programs in already active individuals may have less benefit. Stress reduction is of unclear value.(it is clear. It greatly helps through biofeedback and other found methods) Calcium and potassium supplements have been advocated, but their ability to lower blood pressure is limited and probably not applicable to most patients. (it has been clinically proven to help). Smoking cessation will reduce overall cardiovascular risk.

Antihypertensive Drug Therapy

An ideal antihypertensive drug would be effective as a single agent or in combination with other agents in all classes of patients; would lower blood pressure by a physiologic mechanism; would reduce morbidity and mortality rates; would have no long-term toxicity or unpleasant side effects that affect life-styles; could be taken once a day; would not require multiple-dose titration steps; and would be of moderate cost. No such agent currently exists, but the growing number of available drugs has allowed the physician to tailor treatment to the needs of individual patients.

A. The Stepped Care Approach: In the 1970s and for most of the 1980s, the "stepped care" approach to treatment of hypertension was advocated. Patients were initially started on a diuretic agent, or beta-blocker, and other drugs were added later if required. This approach was highly effective, with approximately 80% of compliant patients exhibiting adequate blood pressure control. Several trials using this approach demonstrated significant reductions in stroke and, in some cases, myocardial infarction and death..

A number of considerations have led some experts to question stepped care as a universal treatment plan. These include the availability of other effective and well-tolerated agents with different mechanisms of action, the recognition that patients not controlled by one agent may respond to another without moving directly to two-drug therapy, and concerns over the long-term implications of metabolic changes observed with diuretics and beta-blockers (especially unfavorable changes in plasma lipids and insulin sensitivity). However, unlike diuretics and beta-blockers, these newer agents have not been proved to prevent the complications of hypertension. Indeed, some of them, such as calcium blockers and alpha-blockers, have not been shown to improve outcomes for any indication. Therefore, the pendulum of opinion has begun to swing back in favor of the drugs with proved benefits.

B. Choice of Initial Medication: Diuretics and beta-blockers should be considered for first-line therapy in most patients, but the choice of medications should be individualized. Additional choices include ACE inhibitors, calcium channel blockers, alpha-blockers, and combined alpha- and beta-blockers. These medications are all effective and generally well tolerated (the alpha-blockers less so), but responses vary among demographic groups. Selection is based upon individual factors, which include age, race, life-style, cost, the experience of the physician, and the side effects of the agent. Accompanying illnesses are often the major factor in selection of medications, since these may exclude some medications or favor the use of others.

C. Current Antihypertensive Agents:

1. Diuretics- The diuretics remain the most widely used antihypertensive medications and are the only agents shown to reduce mortality and morbidity related to coronary artery disease in major trials. Diuretics lower blood pressure initially by decreasing plasma volume (by suppressing tubular reabsorption of sodium, thus increasing the excretion of sodium and water) and cardiac output, but during chronic therapy their major hemodynamic effect is reduction of peripheral vascular resistance by an as yet unknown mechanism. Most of the antihypertensive effect of these agents is achieved at lower dosages than used previously (typically, 25 mg of hydrochlorothiazide or equivalent), but their biochemical effects are dose-related. The thiazide diuretics are the most widely used. The loop diuretics (such as furosemide) may lead to electrolyte and volume depletion more readily than the thiazides and have short durations of action; therefore, they are not ordinarily used in hypertension except in the presence of renal dysfunction (serum creatinine above 2.5 mg/dL). Relative to the beta-blockers and the ACE inhibitors, diuretics are more potent in blacks, older individuals, the obese, and other sub-groups with increased plasma volume or low plasma renin activity. Interestingly, they are relatively more effective in smokers than in nonsmokers. Overall, diuretics administered alone, control blood pressure in 50% of patients and can be used effectively with all other agents. They are perhaps the most effective agents for lowering predominantly systolic hypertension.

The adverse effects of diuretics are relate chiefly to the metabolic changes. Impotence, skin rashes, and photosensitivity are also less frequent side effects. Hypokalemia, with the resulting potential for arrhythmias or renal dysfunction, has been a concern but is uncommon at the usual current dosages (12.5-25 mg hydrochlorothiazide). The risk can be minimized by limiting salt intake or eating a high-potassium diet, and potassium replacement is usually not required to maintain serum K+ at 3.5 mmol/L. Higher serum levels may be prudent in patients at special risk from intracellular potassium depletion (patients taking digoxin or having ventricular arrhythmias and diabetics in whom insulin release and insulin sensitivity are reduced by hypokalemia). It is noteworthy that several of the trials in which diuretic therapy proved most beneficial employed combinations of thiazide and potassium-sparing agents, such as triamterene or amiloride. These medications are more expensive, have additional side effects (primarily gastrointestinal), and may be dangerous in the presence of oliguria. However, it is reasonable to use these agents in appropriate patients receiving higher doses of diuretics and in place of potassium supplements. Diuretics also increase serum uric acid and may precipitate acute gout. Increases in blood glucose, triglycerides, low-density lipoprotein cholesterol, and plasma insulin may occur but are relatively minor during long-term low-dose therapy. Some experts feel that these lipid changes may limit the beneficial effect of blood pressure reduction on the progression of atherosclerosis.

2. Beta-adrenergic blocking agents- These drugs are effective in hypertension because they decrease the heart rate and cardiac output. Even after continued use of beta-blockers for a number of years, cardiac output remains decreased and systemic vascular resistance increased with agents that do not have intrinsic sympathomimetic or alpha-blocking activity. The beta-blockers also decrease renin release and are in general more efficacious in populations likely to have elevated plasma renin activity, such as younger white patients. They neutralize the reflex tachycardia caused by vasodilators such as hydralazine and alpha-adrenergic blockers in the treatment of hypertension. The beta-blockers are especially useful in patients with associated conditions that benefit from this mode of therapy. These include patients with angina pectoris, patients with previous myocardial infarction, and individuals with migraine headaches and somatic manifestations of anxiety.

The side effects of all beta-blockers include development of bronchial asthma in predisposed patients; bradycardia; atrioventricular conduction defects; left ventricular failure; nasal congestion; Raynaud's phenomenon, especially in women; and central nervous system symptoms with nightmares, excitement, and confusion. Fatigue, lethargy, and impotence may occur. All beta-blockers tend to increase plasma triglycerides. The nonselective and, to a lesser extent, the cardioselective beta-blockers tend to depress the protective HDL fraction of plasma cholesterol. This is not seen in agents with intrinsic sympathomimetic activity, and as with diuretics, the changes are blunted with time and dietary changes. Some experts believe that these lipid changes may have an adverse effect on coronary artery disease.

These agents are contraindicated in patients with congestive heart failure or symptomatic bronchospasm. Beta-blockers are relatively contraindicated in insulin-dependent diabetes, since they inhibit gluconeogenesis and may prolong hypoglycemic episodes. However, recent studies have not confirmed earlier suggestions that they may worsen symptoms of peripheral vascular disease.

3. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II blockers- These drugs are being increasingly used as the initial medication in mild to moderate hypertension. Their primary mode of action is inhibition of the renin-angiotensin-aldosterone system, but they also inhibit bradykinin degradation, stimulate vasodilating prostaglandin synthesis, and, sometimes, reduce sympathetic nervous system activity. These latter actions may explain why they exhibit some effect even in patients with low plasma renin activity. The ACE inhibitors appear to be most effective in younger whites. They are relatively less effective in blacks and in the elderly and in predominantly systolic hypertension. While as single therapy they achieve adequate antihypertensive control in only about 40-50% of patients, the combination of an ACE inhibitor and a diuretic or calcium channel blocker is potent.

An advantage of the ACE inhibitors is their relative freedom from troublesome side effects. Severe hypotension can occur in patients with bilateral renal artery stenosis; acute renal failure may ensue. Hyperkalemia may develop in patients with intrinsic renal disease and type IV renal tubular acidosis (commonly seen in diabetics) and in the elderly. A chronic dry cough due to bronchial or laryngeal irritation is seen in 5-15% of patients and may require stopping the drug. Skin rashes and taste alterations are seen more often with captopril than with the non-sulfhydryl-containing agents (enalapril and lisinopril) but often disappear with continued therapy. Angioneurotic edema is an uncommon but potentially dangerous side effect of all agents of this class. Proteinuria and neutropenia are very uncommon at the lower dosages now employed except in individuals with preexisting renal insufficiency or autoimmune disease.

4. Calcium channel blockers- All the agents of this class reduce blood pressure, and a number of new agents with a longer duration of action and perhaps less negative inotropic activity are available. They act by causing peripheral vasodilation, which is associated with less reflex tachycardia and fluid retention than other vasodilators. These agents are effective as single-drug therapy in approximately 60% of patients and appear to be effective in all demographic groups and all grades of hypertension. As a result, they may be preferable to beta-blockers and ACE inhibitors in blacks and older subjects. Calcium channel blockers and diuretics are less additive when given together than when either is combined with beta-blockers or ACE inhibitors. However, verapamil and diltiazem should be combined cautiously with beta-blockers because of their potential for depressing atrioventricular conduction and sinus node automaticity. Several recent reports have raised concern that calcium blocker therapy may be associated with an increased rate of cardiac events. These data primarily apply to short-acting formulations and are limited by their methodology, but nonetheless they highlight the need for prospective clinical trials. Until such data are available, it is prudent not to utilize short-acting formulations and to choose calcium blockers as first-line agents only in appropriately selected individuals.

The most common side effects of calcium channel blockers are headache, peripheral edema, bradycardia, and constipation (especially with verapamil in the elderly). The dihydropyridine agents¾nifedipine, nicardipine, isradipine, felodipine, and amlodipine - are more likely to produce symptoms of vasodilation, such as headache, flushing, palpitations, and peripheral edema. Calcium channel blockers have negative inotropic effects and may cause or exacerbate heart failure in patients with cardiac dysfunction. This tendency may be less with amlodipine. Most of these agents are now available in preparations that can be administered once or twice daily.

5. Alpha-adrenoceptor antagonists- Prazosin, terazosin, and doxazosin block postsynaptic alpha receptors, relax smooth muscle, and reduce blood pressure by lowering peripheral vascular resistance. These agents are effective as single-drug therapy in some individuals, but tachyphylaxis may appear during long-term therapy and side effects are relatively common. The major side effects are marked hypotension and syncope after the first dose, which, therefore, should be small and be given at bedtime. Postdosing palpitations, headache, and nervousness may continue to occur during chronic therapy. These side effects may be less frequent or severe with doxazosin because of its more gradual onset of action. Unlike the beta-blockers and diuretics, the alpha-blockers have no adverse effect on serum lipid levels - in fact, they increase high-density lipoprotein cholesterol while reducing total cholesterol. Whether this is beneficial in the long term has not been established. These drugs are most useful in combination with other agents in less responsive patients. One interesting attribute is a reduction in symptoms of prostatism in some men, which makes these drugs appropriate first-line agents for symptomatic patients.

6. Drugs with central sympatholytic action- Methyldopa, clonidine, guanabenz, and guanfacine lower blood pressure by stimulating alpha-adrenergic receptors in the central nervous system, thus reducing efferent peripheral sympathetic outflow. These agents are effective as single therapy in some patients, but they are usually employed as second- or third-line agents because of the high frequency of drug intolerance, including sedation, fatigue, dry mouth, postural hypotension, and impotence. An important concern is rebound hypertension following withdrawal. Methyldopa also causes hepatitis and hemolytic anemia and should be avoided except in individuals who have already tolerated chronic therapy. Clonidine is available in patches and may have particular value in patients in whom compliance is a troublesome issue.

7. Arteriolar dilators- Hydralazine and minoxidil relax vascular smooth muscle and produce peripheral vasodilation. When given alone, they stimulate reflex tachycardia, increase myocardial contractility, and cause headache, palpitations, and fluid retention. They are usually given in combination with diuretics and beta-blockers in resistant patients. Hydralazine produces frequent gastrointestinal disturbances and may induce a lupus-like syndrome. Minoxidil causes hirsutism and marked fluid retention; this agent is reserved for the most refractory of patients.

8. Peripheral sympathetic inhibitors- These agents are now used infrequently. Reserpine remains a cost-effective antihypertensive agent. Its reputation for inducing mental depression and its other side effects - sedation, nasal stuffiness, sleep disturbances, and peptic ulcers¾have made it unpopular, though these problems are uncommon at low dosages. Guanethidine and guanadrel inhibit catecholamine release from peripheral neurons but frequently cause orthostatic hypotension (especially in the morning or after exercise), diarrhea, and fluid retention. These agents are used chiefly in refractory hypertension.

D. Initiating Therapy

When an initial agent is selected, the patient should be informed of common side effects and the need for diligent compliance. Unless the initial blood pressure is very high (> 180/110), follow-up visits should be at 4- to 6-week intervals to allow for full medication effect to be manifest (especially with diuretics).

E. Combination Therapy

Most patients with hypertension can be controlled with one agent or with two-drug combinations such as (1) a diuretic plus a beta-blocker, (2) a diuretic plus an ACE inhibitor, (3) a diuretic plus a calcium channel blocker, or (4) a calcium channel blocker plus an ACE inhibitor. A minority may require triple-drug therapy. Particularly useful multidrug regimens are (1) a diuretic plus a beta-blocker plus a vasodilator or a calcium channel blocker; (2) a diuretic plus an ACE inhibitor plus either a calcium channel blocker or a sympatholytic (or both); and (3) a calcium channel blocker plus an ACE inhibitor plus either a sympatholytic or a beta-blocker (or both). Patients who are compliant with their medications and who do not respond to these combinations should usually be evaluated for secondary hypertension before proceeding to more complex regimens.

F. Treatment of Hyperlipidemia

A critical element in preventing hypertension-related morbidity is concomitant control of hyperlipidemia.

G. Follow-Up of the Treated Hypertensive

Once blood pressure is controlled on a well-tolerated regimen, follow-up visits can be infrequent and laboratory testing should be limited to tests appropriate for the patient and the medications utilized. During long-term treatment, twice-yearly visits are sufficient for stabilized patients. Testing, in addition to that required for health maintenance, includes renal function and potassium levels for diuretics and ACE inhibitors. In addition, yearly monitoring of blood lipids is recommended in patients with hypertension, and an ECG should be repeated at 2- to 4-year intervals depending on whether initial abnormalities are present, the presence of coronary risk factors, and age.

Patients who have had excellent blood pressure control for several years, especially if they have lost weight and initiated favorable lifestyle modifications, should be considered for "step-down" of therapy to determine if lower doses or discontinuing of medications is feasible.

High Blood Pressure (Hypertension)

Balch

Whether blood pressure is high, low, or normal depends on several factors: the output from the heart, the resistance to blood flow of the blood vessels, the volume of blood, and blood distribution to the various organs. All of these factors in turn can be affected by the activities of the nervous system and certain hormones.

If blood pressure is elevated, the heart must work harder to pump an adequate amount of blood to all the tissues of the body. Ultimately, the condition often leads to kidney failure, heart failure, and stroke. In addition, high blood pressure is often associated with coronary heart disease, arteriosclerosis, kidney disorders, obesity, diabetes, hyperthyroidism, and adrenal tumors.

Because high blood pressure usually causes no symptoms until complications develop, it is known as the "silent killer". Warning signs associated with advanced hypertension may include headaches, sweating, rapid pulse, shortness of breath, dizziness, and visual disturbances.

Blood pressure is usually divided into two categories, designated primary and secondary. Primary hypertension is high blood pressure that is not due to another underlying disease. The precise cause is unknown, but a number of definite risk factors have been identified. These include cigarette smoking, stress, obesity, excessive use of stimulants such as coffee or tea, drug abuse, and high sodium intake. Because too much water retention can exert pressure on the blood vessels, those who consume foods high in sodium may be at a greater risk for high blood pressure. Elevated blood pressure is also common in people who are overweight. Blood pressure can rise due to stress as well, because stress causes the walls of the arteries to constrict. Also, those with a family history may be more likely to suffer from high blood pressure.

When persistently elevated blood pressure arises as a result of another underlying health problem, such as a hormonal abnormality or an inhereted narrowing of the aorta, it is called secondary hypertension. A person may also have secondary hypertension because the blood vessels are chronically constricted or have lost elasticity from a buildup of fatty plaque on the inside walls of the vessel, a condition known as atherosclerosis. Arteriosclerosis and atherosclerosis are common precursors of hypertension. The narrowing and/or hardening of the arteries makes circulation of blood through the vessels difficult. As a result, blood pressure becomes elevated. Secondary hypertension can also be caused by poor kidney function, which results in the retention of excess sodium and fluid in the body. This increase in blood volume within the vessels causes elevated blood pressure levels. The kidneys may also elevate blood pressure by secreting substances that cause blood vessels to contrict.

It is IMPOSSIBLE for a health care provider to make a CORRECT diagnosis of high blood pressure with a single reading. The test must be repeated througout the day to be accurate. home testing is best because it enables you to monitor your condition periodically.

Below are some natural ways to help lower high blood pressure.

NUTRIENTS

SUPPLEMENT	DOSAGE	COMMENTS
calcium	1,500-3,000 mg daily	Deficiencies have been linked to high blood pressure.
magnesium	750-1,000 mg daily	as above
potassium	as directed on label	If you are taking cortisone or high blood pressure medication, take care to adjust for depletion or elevation.
Coenzyme Q10	as directed	Improves heart function
Essential Fatty Acids (black currant seed oil, flaxseed oil, OLIVE OIL, primrose oil)	as directed	Important for circulation and for lowering blood pressure
Garlic	2 capsules 3 times daily	Effective in lowering pressure
L-arginine	as directed	Shown to play an increaseingly important role in heart health by lowering blood pressure and cholesterol levels
L-carnitine	500 mg twice daily, on an empty stomach	Transports long fatty acid chains. Together with L-glutamic acid and L-glutamine, aids in preventing heart disease.
L-glutamic acid	500 mg daily on empty stomach.	as above
L-glutamine	as above	as above
Selenium	200 mcg daily	Deficiency has been linked to heart disease.
Vitamin E	as directed	Improves heart function. Vitamin E also acts as a blood thinning agent; use with caution if you are taking prescription blood thinners. Use d-alpha-tocopherol form.
Vitamin C	3,000-6,000 mg daily in divided doses	Improves adrenal function; reduces blood clotting tendencies
Lecithin Granules	1 tbsp 3 times daily before meals	They emulsify fat, improve liver function, and lower blood pressure
Proteolytic Enzymes	as directed	Aids in cleansing the circulatory system. Completes protein digestion.
Vitamin B complex	100 mg twice daily	Important for circulatory function and for lowering blood pressure
Niacin	50 mg twice daily
Choline	50 mg twice daily
Inositol	50 mg twice daily

RECOMMENDATIONS

1. Follow a strict salt-free diet. This is essential for lowering blood pressure. Lowering your salt intake is not enough; eliminate all salt from your diet. Read labels carefully and avoid those food products that have "salt", "soda", "sodium", or the symbol "Na" on the label. Some foods and food additives that should be avoided on this diet include monosodium glutamate (Accent, MSG); baking soda; canned vegetables (unless marked sodium or salt free); commercially prepared foods; over the counter medications that contain ibuprofen (such as Advil or Nuprin); diet soft drinks; foods with mold inhibitors, preservatives, and/or sugar substitutes; meat tenderizers; softened water; and soy sauce.

2. Eat a high-fiber diet and take supplemental fiber.

3. Eat plenty of fruits and vegetables, such as apples, asparagus, broccoli, cabbage, cantaloupe, eggplant, garlic, grapefruit, green leafy vegetables, melons, peas, prunes, squash, and sweet potatoes.

4. Include fresh "live" juices in the diet. The following juices are healthful: beet, carrot, celery, currant, cranberry, citrus fruit, parsley, spinach, and watermelon.

5. Eat grains like BROWN rice, buckwheat, millet, and oats.

6. DRINK STEAM-DISTILLED WATER ONLY

7. Take 2 tablespoons of flaxseed oil daily

8. AVOID ALL ANIMAL FATS. Bacon, beef, bouillons, chicken liver, corned beef, dairy products, gravies, pork, sausage, and smoked or processed meats are prohibited. The only acceptable animal foods are broiled white fish and skinless turkey or chicken that has been raised hormone and antibiotic free. Get protein from vegetable sources, grains, and legumes instead.

9. Avoid foods such as aged cheeses, aged meats, anchovies, avocados, chocolate, fava beans, pickled herring, sherry, sour cream, wine, and yogurt.

10. Avoid all alcohol, caffeine, and tobacco

11. If you are taking an MAO inhibitor, avoid the chemical tyramine and its precursor tyrosine. Combining MAO inhibitors with tyramine causes the blood pressure to soar and could cause a stroke. Tyramine-containing foods include almonds, avocados, bananas, beef or chicken liver, beer, cheese, chocolate, coffee, fava beans, herring, meat tenderizers, peanuts, pickles, pineapples, pumpkin seeds, raisins, sausage, sesame seeds, sour cream, soy sauce, wine, yeast extracts, yogurt, and other foods. In general, any high protein fod that has undergone aging, pickling, fermentation, or similar processes should be avoided. Over the counter cold and allergy remedies should also be avoided.

12. Keep your weight down.

13. Fast for three to five days each month. Periodic cleansing fasts help to detoxify the body.

14. Get regular light to moderate exercise. Take care not to overexert yourself.

15. Be sure to get sufficient sleep.

16. Do not take antihistamines.

17. Avoid the artificial sweetener aspartame (Equal, Nutrasweet) which contains phenylalanine.

18. As much as possible, avoid stress.

THINGS TO CONSIDER

1. Because the use of diuretic drugs causes increased urinary excretion of magnesium, it can cause hypomagnesemia in people. Magnesium is needed in conjunction with calcium to prevent bone deterioration, as well as to maintain a normal heart rhythm and muscular contraction. Loss of potassium dure to diuretics may be dangerous, causing heart malfunction. Herbal diuretics are far safer.

2. People with hypertension often suffer from sleep apnea, in which they stop breathing for ten seconds or more throughout the night. Apnea is associated with loud snoring and restless sleep, and can cause the individual to feel excessively sleepy during the day.

3. According to the National Stroke Association, hypertension is the most important controllable risk factor for stroke, increasing the risk of stroke by seven times.

4. Approximately 80 million Americans have increased sensitivity to dietary sodium. African-Americans in particular are prone to salt-sensitive hypertension.

5. Heavy snorers are more likely to have high blood pressure or angina than silent sleepers. Research suggests that snorers may suffer from a malfunctioning of the part of the brain responsible for fluent breathing; this can put an unnatural strain on the heart and lungs due to oxygen shortage.

6. Researchers at the State University of New York found that the lower the level of magnesium in the body, the higher the blood pressure. This double-blind, placebo-controlled trial showed that taking supplemental magnesium can result in a significant, dose-dependent reduction in both systolic and diastolic blood pressure.

7. Apple pectin aids in reducing blood pressure.

8. Certain colors have a beneficial effect on blood pressure. (see Color Therapy). Music also can be used to reduce stress and thereby lower blood pressure.

9. Taking medication for high blood pressure may lead to low blood pressure (hypotension). Hypotension can cause fainting, fatigue, and weakness, possibly with nausea, sweating, and restlessness preceding a loss of consciousness. Postural hypotension, which is a very temporary lowering of blood pressure, is usually caused by standing up too suddenly. This leads to dizziness and wears off quickly. For older adults, low blood pressure can simple result from eating. This is called postprandial hypotension, and it happens because blood is diverted to the gastrointestinal tract to help with digesting the food. In older people, the heart is not as efficient at increasing blood flow by pumping more quickly, so, with too much blood going to help with digesting a meal, there is too little traveling to the brain. Drinking lots of fluids increases blood volume, which may alleviate this condition.

Natural Approach to Hypertension

Farhang Khosh, ND, Mehdi Khosh, ND

Abstract

Hypertension is a common problem facing many Americans today, with two million new cases being diagnosed each year. Although billions of dollars are spent annually in the United States for the treatment and detection of cardiovascular disease, current conventional treatments have done little to reduce the number of patients with hypertension. Alternative medicine offers an effective way to decrease the rising number of people with high blood pressure. Research has found a variety of alternative therapies to be successful in reducing high blood pressure including diet, exercise, stress management, supplements, and herbs. (Altern Med Rev 2001:6(6):590-600)

Introduction

Hypertension is one of the leading causes of disability or death, due to stroke, heart attack, and kidney failure. Expenses related directly or indirectly to the treatment and detection of hypertension in the United States are approximately $10 billion yearly. Heart disease and stroke remain the first and third leading causes of death, respectively, in the United States. Despite the importance of these observations, for many people blood pressure is poorly controlled. (1 )

An estimated 50 million American adults (25 percent of all adults) have high blood pressure, but only 68 percent are aware of their condition, and only 27 percent have it under control. (2) Each year, two million new cases of hypertension are diagnosed.(3) The risk of hypertension increases with age in both men and women.( 4) Before age 55, more men than women have hypertension; the reverse is true for those over the age of 55. African Americans have significantly more risk of developing high blood pressure then Caucasians and Mexican Americans.

There are two types of high blood pressure: essential (primary) hypertension and secondary hypertension. Essential hypertension does not have a readily identifiable cause, and is the most common type of hypertension, accounting for 90 percent of all cases of high blood pressure. Genetics play a major role in essential hypertension. In the case of secondary hypertension, the cause can be identified and is usually treatable or reversible.

Optimal blood pressure (BP) is 120/80 mm Hg or less. (5) The systolic pressure measures the force that blood exerts on the artery walls as the heart contracts to pump blood, while the diastolic pressure measures the force when the heart relaxes to allow blood flow into the heart.

Beta-blockers, diuretics, or both are usually the first line of treatment for most physicians. (7)

Dietary Approaches to Hypertension

A diet low in saturated fat and high in complex carbohydrate is recommended. Such a diet includes whole grains, fruits, vegetables, nuts, seeds, legumes, fish, soy products, onions, garlic, foods rich in potassium, calcium, and magnesium (carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, broccoli, and most fruits), and restricts salt.

Subjects (n=133) were enrolled in the Dietary Approaches to Stop Hypertension (DASH) trial in order to determine the effect of diet on blood pressure. Systolic blood pressures of participants ranged from 140-159 mm Hg, while diastolic BPs were 90-95 mm Hg. Subjects ate a control diet for three weeks before being randomized to receive either a diet rich in fruits and vegetables, that same diet but with elimination of red meat, sugar, and reduced in fats, or a control diet for another eight weeks. The low-fat, low-sugar diet rich in fruits and vegetables significantly reduced both systolic and diastolic BP. While the fruits-and-vegetables diet also significantly reduced systolic and diastolic blood pressures, the combination diet produced greater BP-lowering effects; changes were evident within two weeks of starting the diet. By the end of the eight-week trial, 70 percent of participants eating the combination diet had a systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg, compared with 45 percent on the diet rich in fruits and vegetables and 23 percent on the control diet.(8)

Lifestyle Changes

More than one-third of the adult population of the United States is obese,(9) presenting a significant risk factor for hypertension. Many studies have shown obese hypertensive patients can reduce their medication with weight loss. A sedentary individual has a 35-percent greater risk of developing hypertension than does an athlete.(6)

One study found insufficient sleep can contribute to increased blood pressure in hypertensives. The researchers theorized this may be due to increased sympathetic nervous activity during the night.(10)

Stress management and relaxation techniques such as meditation can help in controlling high blood pressure. In one study researchers found nearly 70 percent of patients with mild to moderate hypertension using techniques to reduce stress were able to reduce their medication after six weeks; after one year, 55 percent required no medication.(11)

Specific Nutrient Supplementation

Minerals: Potassium and Magnesium

Potassium is one of the most important minerals for hypertension. It is well documented that a diet low in potassium and high in sodium is associated with hypertension. (12-17)

There have been several studies indicating magnesium (Mg) may help to lower blood pressure and even prevent hypertension. Its hypotensive effect is thought to be due to relaxation of the smooth muscles of the blood vessels. A recent study demonstrated magnesium supplementation prevented blood pressure elevation in hypertensive rats. Magnesium's mechanism of action was theorized to be associated with inhibition of platelet calcium uptake and decrease in intracellular free calcium concentrations.(18) In another study, researchers showed that taking magnesium in amounts as low as 365 mg per day with beta blockers can significantly reduce blood pressure compared to taking beta blockers alone.(19)

In a double-blind cross-over study of magnesium in hypertension, 17 subjects (diastolic BPs > 90 mm Hg) were supplemented with 15 mM Mg daily for three weeks, 30 mM Mg for another three weeks, and ending with 40 mM Mg for a final three weeks. Statistically significant decreases in average systolic and diastolic BPs were noted. (20)

Coenzyme Q10

Studies have clearly shown the potential benefit of coenzyme Q10 (CoQ10) in treatment of hypertension and congestive heart failure.(21-25) In one study, 109 patients with essential hypertension were supplemented with CoQ10 at an average oral dose of 225 mg/day in addition to their existing antihypertensive drug regimen. Eighty percent of patients in the study had been diagnosed with hypertension for an average of 9.2 years. Dosage was dependant on blood levels of CoQ10, the objective being to maintain blood levels of greater than 2.0 mcg/mL. Patients were gradually able to decrease antihypertensive drug therapy during the first one to six months. Fifty-one percent of patients were able to completely discontinue between one and three antihypertensive drugs an average of 4.4 months after starting CoQ10.(26)

In addition to normalizing blood pressure, another study found that CoQ10 may also be effective in reducing total cholesterol. In this study 26 hypertensives were supplemented with CoQ10 at a dose of 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and HDL cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure decreased from an average of 164 mm Hg to 146 mmHg, while diastolic blood pressure decreased from an average of 98 mm Hg to 86 mm Hg. Average serum total cholesterol decreased slightly, from 222 mg/dL to 213 mg/dL, while there was no significant change in HDL levels.(27) Long term studies on safety of CoQ10 have shown it to be a safe supplement.22 It may take as long as 4-12 weeks to note significant results.

Omega-3 Fatty Acids

Increasing the intake of omega-3 fatty acids can lower blood pressure.28 Recent research suggests that the omega-3 fatty acid, eicosapentanoic acid (EPA), directly modulates intracellular calcium ion (Ca2+) signaling in vascular smooth muscle cells, resulting in a vasodilation effect and lowering of blood pressure.(29-31)

Sixteen mild essential hypertensive male outpatients and 16 normotensive male controls were randomly assigned to receive either EPA and docosahexanoic acid (DHA) (2.04 g EPA and 1.4 g DHA) or olive oil (4 g/day) as a placebo for a period of four months. The effect of omega-3 fatty acids on blood pressure in the treatment group was maximized after two months with systolic BP decreasing an average of 6 mm Hg, (p<0.05) and diastolic blood pressure down an average of 5 mm Hg, (p<0.05).(32) Omega-3 oils are also effective in lowering triglycerides and LDLs, and increasing HDLs.

In a double-blind placebo-controlled study of 935 patients with hypertriglyceridemia and hypertension, researchers found omega-3 oil supplementation resulted in significant reductions in total cholesterol and blood pressure and significant increase in HDL (an overall mean rise of 7.4 percent).(33) In addition, omega-3 oils can prevent primary or secondary coronary heart disease.(34-37)

Amino Acids: L-Arginine and Taurine

L-arginine is a precursor to nitric oxide (endothelial-derived relaxing factor) which dilates blood vessels and lowers blood pressure. Several studies have shown that inhibiting the synthesis of nitric oxide in animal models results in hypertension.(38)

Dietary L-arginine supplementation has been proposed to reverse endothelial dysfunction in certain conditions, including hypercholesterolemia, coronary heart disease, and some forms of animal hypertension. Chronic oral administration of L-arginine prevented the blood pressure rise induced by sodium chloride loading in salt-sensitive rats.(39)

A single-blind, controlled, crossover dietary intervention was conducted on six healthy subjects in order to assess the effects of an L-arginine enriched diet on blood pressure. The subjects randomly received three different diets, each for a period of one week: 1) a control; 2) a natural foods diet enriched with L-arginine; or 3) a diet identical to the control diet with the addition of L-arginine supplementation. A decrease in BP was observed with both L-arginine-enriched diets. In addition, creatinine clearance was improved and fasting blood sugar decreased by the addition of L-arginine.(39)

Taurine, a sulfur-containing amino acid, has been reported to have antihypertensive and sympatholytic activity.(40) Nineteen patients with borderline hypertension were supplemented with 6 g taurine daily for seven days in a double-blind, placebo-controlled study. Systolic BP in the 10 taurine-treated patients decreased an average of 9 mm Hg compared with a 2 mm Hg decrease in the nine patients treated with placebo; diastolic BP in the taurine-treated patients decreased an average of 4 mm Hg compared with 1 mm Hg in the placebo-treated subjects. Taurine supplementation resulted in a significant decrease in plasma epinephrine but not norepinephrine levels. Individuals with hypertension tend to have higher epinephrine compared to people with normal blood pressure.(41) Research shows taurine relaxes blood vessels by enhancing endorphin production, resulting in lowered blood pressure.(42,43)

Vitamins C and E

Vitamins C and E may both play a beneficial role in the prevention and treatment of hypertension. Vitamin C has the potential to impact defective endothelium-dependent vasodilation. Although the mechanism has not been fully elucidated, it is believed that ascorbic acid functions as an antioxidant to either enhance the synthesis or prevent the breakdown of nitric oxide.(44) A 1999 Lancet randomized, double-blind, placebo-controlled study showed that treatment of hypertensive patients with vitamin C lowered blood pressure. Thirty-nine patients received either ascorbic acid (n=19) or placebo (n=20) in a one-time dose of 2 g, followed by 500 mg daily for 30 days. Mean systolic blood pressure decreased from 155 mm Hg to 142 mm Hg (p<0.001) after 30 days in the ascorbate group, while placebo had no effect. Mean diastolic BP decreased in the ascorbate group after one month but was not significantly different than placebo. There was no significant effect in blood pressure after the initial 2 g dose.(45)

Vitamin E has also been found to increase nitric oxide synthase activity, resulting in lowered blood pressure in hypertensive patients. An animal study found that for all alpha-tocopherol-treated groups, blood pressure was significantly reduced compared to a hypertensive control group; maximum reduction of blood pressure was achieved at a dosage of 34 mg alpha-tocopherol/kg diet.(46)

Specific Botanicals for Hypertension

Hawthorne (Crataegus oxycantha and monogyna)

Hawthorne has been used traditionally for cardiovascular disorders in many cultures. It contains a number of active constituents including flavonoids, catechins, triterpene saponins, amines, and oligomeric proanthocyanidins (OPCs). Hawthorne has been shown to exert a mild blood pressure lowering effect(47,48) that can take up to four weeks for maximal results. It is believed that the herb dilates coronary blood vessels.(48) One in vitro study on rat aorta found proanthocyanidins extracted from hawthorne relaxed vascular tone via endothelium-dependent nitric oxide-mediated relaxation.(49)

Arjuna Bark (Terminalia arjuna)

Terminalia arjuna is a deciduous tree found throughout India. Its bark has been used in Ayurvedic medicine for over three centuries. Terminalia's active constituents include tannins, triterpenoid saponins, flavonoids, gallic acid, ellagic acid, OPCs, phytosterols, calcium, magnesium, zinc, and copper.(50) Several studies have elucidated Terminalia's effects on various cardiac disorders including congestive heart failure, coronary artery disease, and hypertension. A study on its effects on stable and unstable angina patients found it effective for those with stable angina, with a 50-percent reduction in angina episodes and significant decrease in systolic blood pressure.(51)

In a double-blind crossover study, 12 subjects with refractory chronic congestive heart failure (idiopathic dilated cardiomyopathy (n=10); previous myocardial infarction (n=1), or peripartum cardiomyopathy (n=1)), received Terminalia arjuna, at a dose of 500 mg every eight hours, or placebo for two weeks, each treatment protocol separated by a two-week washout period, as an adjuvant to conventional therapy. Clinical, laboratory, and echocardiographic evaluations were carried out at baseline and at the end of therapy. Terminalia, compared to placebo, was associated with improvement in symptoms and signs of heart failure, decrease in echo-left ventricular end diastolic and end systolic volume indices, increase in left ventricular stroke volume index, and increase in left ventricular ejection fractions.(52) A study with similar dosing on primarily post-myocardial infarction angina patients found improvements in cardiac function. Prolonged use resulted in no adverse side effects or signs of renal, hepatic, or hematological abnormalities.(53)

Olive Leaf (Olea africana and Olea europea)

Olive leaf extract is derived from the leaves of the olive tree. The entire leaf extract contains several phytochemicals, including 20-percent oleuropein, a complex structure of flavonoids, esters, and multiple iridoid glycosides, which acts as a vasodilator, lowering blood pressure and preventing angina attacks. Oleuropein is also being recognized as a potent antioxidant.(54,55) The hypotensive action of olive leaf has been studied for two decades. A clinical study of Olea europaea L. aqueous extract was conducted on two groups of hypertensive patients, 12 patients consulting for the first time, and 18 patients on conventional antihypertensive treatment. An aqueous extract was given for three months, after 15 days of placebo supplementation. Researchers noted a statistically significant decrease of blood pressure (p<0.001) for all patients, without side effects.(56)

One of olive leaf's mechanisms of action is vasodilation. In an in vitro study a decoction of olive leaf caused relaxation of isolated rat aorta endothelium. The relaxant activity was independent of the integrity of the vascular endothelium. Oleuropeoside was found to be a component responsible for vasodilator activity; however, the researchers felt at least one other principle was either a vasodilator itself or potentiated the relaxant effect of oleuropeoside.(57)

European Mistletoe (Viscum album)

The use of mistletoe in medicine has become popular, not only because of its hypotensive activity, but also because of its anticancer properties. Mistletoe is known to possess hypotensive, cardiotonic, vasodilatory, antispasmodic, tumor-inhibiting, and thymus-stimulating activity.(58) Its pharmacological effects, including diuretic and hypotensive activity, were studied using an alcohol extract of Japanese and European mistletoe. Both extracts showed blood pressure lowering effects when administered intravenously and orally to cats.(59) Other researchers have reported similar hypotensive effects of mistletoe in experimental animal studies.(60)

Yarrow (Achillea wilhelmsii)

Achillea wilhelmsii C. Koch (Asteraceae) has flavonoids and sesquiterpene lactone constituents, which have been found effective in lowering blood pressure and lipids. A double-blind, placebo-controlled trial examined the antihyperlipidemic and antihypertensive effects of Achillea. The researchers randomly selected 120 men and women, aged 40-60 years, and divided them into two groups: (1) moderate hyperlipidemic and (2) hypertensive subjects. Each study group was treated either with an alcohol extract of Achillea or placebo at a dose of 15-20 drops twice daily for six months. Blood pressure and serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured at the end of two, four, and six months. A significant decrease was noted in triglycerides after two months, and significant decreases in triglycerides and total- and LDL-cholesterol after four months. Levels of HDL-cholesterol were significantly increased after six months' treatment. A significant decrease was observed in diastolic and systolic blood pressure after two and six months, respectively (p<0.05).(61)

Black Cumin Seeds (Nigella sativa)

Nigella sativa (Ranunculaceae) has a long history of use in folk medicine as a diuretic and hypotensive agent. In an animal study, an oral dose of either Nigella sativa extract (0.6 mL/kg/day) or furosemide (5 mg/kg/day) significantly increased diuresis by 16- and 30 percent, respectively, after 15 days of treatment. In the same rat study, a comparison between Nigella sativa and nifedipine found mean arterial pressure decreased by 22- and 18 percent in the Nigella sativa and nifedipine treated rats, respectively.(62)

The essential oil of Nigella sativa seed has an antioxidant property that makes it useful in treating cardiovascular disorders. Active constituents of Nigella sativa are thymoquinone, dithymoquinone, thymohydroquinone, thymol,(63) carvacrol, t-anethole and 4-terpineol. Hypotensive action of Nigella is mainly due to its volatile oils. An animal study found the volatile oil has the potential of being a potent, centrally acting antihypertensive agent.(64) Thin-layer chromatography (TLC) has confirmed Nigella's antioxidant properties.(65)

Forskolin (Coleus forskohlii)

Coleus forskohlii has been used in Ayurvedic medicine for many years. In 1974 the Indian Central Drug Research Institute discovered that forskolin, a component of this plant, has hypotensive and antispasmodic action. Forskolin's blood pressure lowering effects appear to be due to relaxation of arterial vascular smooth muscle. In a study with isolated heart tissue, forskolin activated membrane-bound adenylatecyclase and cytoplasmic cAMP-dependent protein kinase. The researchers postulated the positive inotropic effect was via an enhanced calcium uptake by the heart muscle cell.(66) Another constituent from Coleus, ditermene coleonol, has been found to lower blood pressure in both rat and cat models.(67)

Indian Snakeroot (Rauwolfia serpentina)

Rauwolfia is cultivated for the medicinal use of its 30 alkaloids (particularly reserpine found in the root), many used in treating hypertension.(68) Besides reserpine, other alkaloids used in hypertension and other cardiac disorders are ajmaline, rescinnamine, serpentinine, sarpagine, deserpidine, and chandrine. Rauwolfia alkaloids work by controlling nerve impulses along certain pathways that affect heart and blood vessels, lowering blood pressure. Rauwolfia depletes catecholamines and serotonin from nerves in the central nervous system.(69) In a controlled intervention trial, 389 subjects, ages 21-55 years, with diastolic blood pressures 90-115 mm Hg were examined for 7-10 years. Subjects were randomly assigned to either a combination of a diuretic and Rauwolfia serpentina, or an identical placebo. Diastolic blood pressure was reduced an average of 10 mm Hg and systolic by16 mm Hg in the active treatment group, with no change in the placebo group.(70)

The Rauwolfia constituent ajmaline not only lowers blood pressure, but also has a potent antiarrhythmic effect. Studies have shown that ajmaline specifically depresses intraventricular conduction, suggesting this would be particularly effective in the treatment of re-entrant ventricular arrhythmias.(71,72)

In one study of 100 patients with essential hypertension, it was determined that serum cadmium levels were 43-percent higher and serum zinc levels 28-percent lower in hypertensives when compared with normotensive controls. When the patients were put on ajmaloon, a preparation from Rauwolfia serpentina, blood pressure was lowered significantly. It also appeared to decrease the elevated serum cadmium levels in these individuals.(73)

Garlic (Allium sativum)

Garlic is eaten in Asia, the Middle East, and in many other cultures on a daily basis. It is an ancient home remedy that has been used for many different purposes, including hypertension, and reduces a number of risk factors associated with cardiovascular disease including: 1) reducing total and LDL-cholesterol, 2) increasing HDL-cholesterol, 3) lowering triglycerides and fibrinogen, 4) lowering blood pressure, 5) improved circulation, 6) enhancing fibrinolysis, 7) inhibition of platelet aggregation, and 8) reducing plasma viscosity. The blood pressure effect is thought to be due to an opening of (Ca) ion channels in the membrane of vascular smooth muscle, affecting hyperpolarization, resulting in vasodilation.(74) A garlic preparation containing 1.3-percent allicin at a large dose (2400 mg) was evaluated in an open-label study in nine severely hypertensive patients (diastolic blood pressure 115 mm Hg or greater). Approximately five hours after taking the garlic, the systolic blood pressure fell an average of 7 mm Hg while diastolic BP dropped an average of16 mm Hg. A significant decrease in diastolic blood pressure lasted from 5-14 hours after the dose and no significant side effects were reported.(75)

Conclusion

Lifestyle change, including diet, exercise, and stress management, may contribute significantly to lowering of blood pressure. Supplements such as potassium, magnesium, CoQ10, omega-3 fatty acids, amino acids L-arginine and taurine, and vitamins C and E have been effectively used in the treatment of cardiovascular disease, including hypertension. Botanicals have been used for centuries to treat various diseases including cardiovascular disorders. It is no surprise they have proven effective in lowering blood pressure and improving heart function. Among the most researched and frequently utilized for hypertension are hawthorne, Terminalia arjuna, olive leaf, European mistletoe, yarrow, black cumin seeds, forskolin, Indian snakeroot, and garlic. More research is indicated to determine the full potential that alternative medicine has to offer in the management of hypertension. With the increasing numbers of patients suffering from hypertension and conventional medicine failing to effectively control the problem, alternative therapies offer hope.

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Sodium Induces Hypertrophy of Cultured Myocardial Myoblasts and Vascular Smooth Muscle Cells

(The following study may be a great reason to cut down on sodium when trying to lower blood pressure)

Jian-Wei Gu; Vivek Anand; Eugene W. Shek; Michael C. Moore; Ann L. Brady; Whitney C. Kelly; ; Thomas H. Adair

From the Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center (Jackson).

Correspondence to Dr Thomas H. Adair, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, Mississippi 39216-4505. E-mail thadair@fiona.umsmed.edu

Abstract—The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers reached 80% confluence, normal sodium medium (146 mmol/L) was replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the higher concentrations for 5 days caused dose-related increases in cell mean diameter, cell volume, and cellular protein content in both MMbs and VSMCs. Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L) caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and 46.7% increase in cellular protein content. The rate of protein synthesis, expressed as [3H]leucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146-mmol/L sodium control group. Exposure of MMbs to medium with a sodium concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease (range, 26% to 44%) in the rate of protein degradation at multiple time points over a 48-hour period compared with normal sodium control cells. The increase in cellular protein content caused by 160 mmol/L sodium returned to normal within 3 days after MMbs were returned to a normal sodium medium. These findings support the hypothesis that sodium has a direct effect to induce cellular hypertrophy and may therefore be an important determinant in causing myocardial and/or vascular hypertrophy in subjects with increased sodium concentration in the extracellular fluid.

Recommendations for Hypertension:

Amino Acid / Protein

Theanine (L-Theanine): High blood pressure is a feature of stress that can be lowered by lowering the stress. The simple act of drinking a cup of tea (which contains theanine) can lower blood pressure by forcing a person to slow down and relax.

Animal-based

Fish Oils: In a review of 36 clinical studies, just under 4gm of fish oil per day was associated with modest reductions in both systolic and diastolic pressure, especially if subjects were older and had hypertension. [Journal of Hypertens 2002;20(8): pp.1493-1499]

Botanical

Gingko Biloba: One effect of Ginkgo extract is that of promoting vasodilation and blood flow.

Chlorella / Algae Products: Fifty-five subjects with fibromyalgia, 33 with hypertension, and 9 with ulcerative colitis consumed 10gm of pure chlorella in tablet form and 100mL of a liquid containing an extract of chlorella each day for 2 or 3 months. Daily dietary supplementation with chlorella was seen to reduce high blood pressure, lower serum cholesterol levels, accelerate wound healing and enhance immune functions. Researchers concluded that the potential of chlorella to relieve symptoms, improve quality of life, and normalize body functions in patients with fibromyalgia, hypertension, or ulcerative colitis suggests that larger, more comprehensive clinical trials of chlorella are warranted. [Altern Ther Health Med. 2001 May-Jun; 7(3): pp.79-91. Review]

Garlic: One study found that aged garlic extract at 7.2gm per day reduced total and LDL cholesterol, as well as systolic and diastolic blood pressure.

Noni: Research indicates that noni stimulates the immune system, regulating cell function and cellular regeneration of damaged cells. The fact that noni seems to operate on the very basic and critical cellular level may explain why it is useful for a wide variety of conditions. Limited animal studies have been done and some human cancer studies are underway. Most of the evidence for its use is anecdotal. Since many noni products are sold via multilevel marketing, some caution is necessary regarding exaggerated claims.

Mistletoe (Viscum album): Mistletoe is known to relieve pain from headaches caused by high blood pressure. Mistletoe reduces the heart rate, and at the same time strengthens the capillary walls. Its cardiotonic action is thought to be due to the lignans, while the hypotensive action is believed to be due to a choline derivative related to acetylcholine. Choline derivatives bring about parasympathetic stimulation and vasodilatation.

Stephania tetrandra: Stephania tetrandra is a Chinese medicinal herb also known as han-fang-chi or fen-fang-qi. In the Chinese Pharmacopoeia, the herb is recommended for treating general symptoms such as inflammation, fever, and pain; however, it also has been used extensively to manage water retention and edema, eliminate stagnant bronchial mucous, and detoxify. For the past 50 years, however, stephania has been used in China principally as an agent to control blood pressure. Although its use in humans has been limited to China, stephania has been studied in animal models in laboratories throughout the world, and many of its pharmacological properties are relatively well described.

Diet

Weight Loss: At least a half dozen controlled studies of patients with hypertension concluded that short-term weight loss is usually associated with a reduction of blood pressure. In patients who experienced a weight loss of 11.7 kg ( about 25.7 lbs), an average blood pressure reduction of -20.7/-12.7mm Hg was recorded. A similar study found that a decrease in blood pressure of -2.5/-1.5mm Hg per kilogram of reduction of weight, and further demonstrated a significant correlation between weight change and blood pressure change.

Category	Systolic Blood Pressure (mm Hg)	Diastolic Blood Pressure (mm Hg)	Follow-Up Recommended
Optional	<120	<80	Recheck in 2 years
Normal	<130	<85	Recheck in 2 years
High Normal	130-139	85-90	Recheck in 1 year ***
Hypertension Stage 1 (mild)	140-159	90-99	Confirm within 2 months
Stage 2 (moderate)	160-179	100-109	Evaluate or refer within 1 month
Stage 3 (severe)	>180	>110	Evaluate or refer within 1 week