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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main hemodynamic disturbance occurring in patients with essential hypertension is an increase in the total peripheral resistance. In young patients with hypertension, this disturbance is clearly seen during muscular exercise, even though the calculated resistance might be normal during rest. This article reports results of studies on the long-term hemodynamic effects of two calcium channel blockers, verapamil and nifedipine, in patients with mild to moderate hypertension. Twenty-five men, aged 20 to 64 years, with diastolic blood pressures between 100 and 120 mm Hg before treatment were studied at rest and during exercise on ergometer bicycles. Blood pressure was recorded intra-arterially, and cardiac output was measured. After this initial study, 10 patients were treated with verapamil (from 40 to 80 mg, three times daily) and 15 patients with nifedipine (long-acting form, from 40 to 80 mg daily). After one year, the hemodynamic study was repeated. Both drugs induced a reduction in blood pressure and in the total peripheral resistance without any reduction in the cardiac index. Verapamil reduced heart rate, particularly during exercise, but this effect was compensated by an increase in the stroke volume. The hemodynamic profile of these two calcium channel blockers clearly differs from the hemodynamic effects of beta blockers.
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PMID:Hemodynamic effects of calcium channel blockers at rest and during exercise in essential hypertension. 405 Aug 41

Renal plasma flow, glomerular filtration rate plasma angiotensin II, aldosterone and arginine vasopressin, free water clearance, blood pressure and body weight in 11 patients with mild to moderate hypertension were determined at the end of consecutive 6 week periods of administration of placebo and verapamil up to 120 mg t.i.d. Verapamil induced a 10% reduction in diastolic blood pressure. Compared with placebo none of the other parameters measured changed after treatment with verapamil. There was no significant correlation between blood pressure and arginine vasopressin in plasma. It is concluded that verapamil reduced blood pressure by vasodilatation without activation of the counterbalancing mechanisms commonly seen after treatment with vasodilating drugs, i.e. tachycardia, activation of the renin-angiotensin-aldosterone system, water and salt retention, and without affecting renal haemodynamics. AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension.
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PMID:Effect of verapamil on renal plasma flow, glomerular filtration rate and plasma angiotensin II, aldosterone and arginine vasopressin in essential hypertension. 407 25

The relative efficacies of oral verapamil, a calcium-entry blocking drug, and propranolol, a beta-adrenergic blocking drug, were compared in 12 patients who had both stable angina pectoris and mild to moderate systemic hypertension, using a placebo-controlled, double-blind, randomized crossover protocol. Compared with placebo, both propranolol and verapamil decreased the frequency of anginal attacks and the number of nitroglycerin tablets consumed, and increased exercise duration and total work; there were no significant differences in the antianginal effect of the two drugs. Both verapamil and propranolol reduced the supine and standing systolic and diastolic blood pressure measured at rest; compared with propranolol, however, verapamil had greater effects on standing diastolic blood pressure (p less than 0.002). Resting heart rate was reduced from placebo baseline with large doses of both drugs; compared with verapamil, however, propranolol exerted greater effects on resting heart rate and rate-pressure product. Plasma renin activity was increased from placebo baseline with verapamil (p less than 0.05), but was reduced with propranolol (p less than 0.05); no significant change in plasma aldosterone was seen with either drug. Verapamil appears to be a safe and effective treatment alternative to propranolol for relieving anginal symptoms, improving exercise tolerance, and reducing elevated systemic blood pressure in patients with both angina pectoris and mild to moderate systemic hypertension.
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PMID:Comparison of oral propranolol and verapamil for combined systemic hypertension and angina pectoris. A placebo-controlled double-blind randomized crossover trial. 612 46

The calcium antagonist drug, verapamil, was compared in double-blind, double-dummy, crossover studies with two beta-adrenoceptor blocking drugs, pindolol and labetalol. All were equally effective as antihypertensive drugs in patients with mild-to-moderate hypertension. Verapamil caused a fall in blood pressure by reducing total peripheral resistance, as judged by echocardiographic studies, and had no adverse effects on airways resistance in patients with obstructive airways disease. The favorable hemodynamic effects and absence of serious side effects suggest that verapamil may be an important advance in the treatment of hypertension.
Hypertension
PMID:Comparison of beta-adrenoceptor blockers and calcium antagonists in hypertension. 613 71

The role of calcium in the relaxations evoked by methacholine and A23187 in intact rabbit aortic rings was investigated. Methacholine (10(-8) to 10(-6) M) and the calcium ionophore A23187 (10(-8) to 10(-6) M) produced dose-dependent relaxations of rings which had been contracted with the alpha-adrenergic agonist phenylephrine. The ability of a ring to relax in this manner was correlated with the presence of endothelium as judged by transmission and scanning electron microscopy. Purposely disrupting the endothelium led to a loss of the relaxation response. In these rings methacholine caused dose-dependent contractions at concentrations greater than 10(-7) M. Deletion of Ca++ from the incubation medium inhibited maximum methacholine-induced relaxations by 67% and A23187-induced relaxations by 92%. The Ca++-channel blockers verapamil (10 microM) and nifedipine (0.5 microM) inhibited maximum methacholine-induced relaxations by 39% and 45%, respectively. The blockers had no effect on the methacholine ED50 (2.5 x 10(-7) M) for relaxation. Verapamil and nifedipine also inhibited maximum A23187-induced relaxations by 43% and 47% with no effect on the ED50 (6 x 19(-8) M) for relaxation. A structurally dissimilar vasodilator, sodium nitroprusside (10(-7) M), had no effect on the A23187-induced relaxation. These data are consistent with a role of Ca++ in regulating either the production or release of endothelial-derived relaxing factor(s).
Hypertension
PMID:Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. 627 3

The chief site of action of the calcium antagonist drugs is the slow calcium channel in two tissues: the atrioventricular node and vascular smooth muscle. The exact mode whereby these agents work is still unknown, but recently studies with radioligands suggest that the binding site for the dihydropyridines such as nifedipine is different from the site for the verapamil group (including diltiazem). In some way these agents 'close' or 'block' the calcium channels. Verapamil and diltiazem are active against the calcium channel of the atrioventricular node which nifedipine in clinical doses is not; in contrast, nifedipine is more active on peripheral vascular arterial muscle, presumably inhibiting the calcium channel more strongly. An intracellular site of action of these agents on calmodulin in vascular smooth muscle cannot be excluded. Clinically, the chief calcium antagonists (verapamil, nifedipine, diltiazem) constitute a powerful group of cardioactive agents with a spectrum of therapeutic actions rather similar to beta-adrenoceptor blockade, being effective in angina of effort and rest, and hypertension. Critical differences are dependent on the individual properties of the calcium antagonists. Thus only verapamil and diltiazem are effective in inhibiting the AV node while the dihydropyridines such as nifedipine are only vasodilators in clinical doses. As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed.
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PMID:Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review. 632 68

Calcium antagonists have recently emerged as a class of drugs for the treatment of angina, hypertension and certain cardiac arrhythmias. Verapamil is the prototype calcium antagonist and has the most clearly defined antiarrhythmic properties. Other agents in the class include D-600 (gallopamil), tiapamil, nifedipine, and diltiazem. The antiarrhythmic effects of these compounds can be correlated with their electrophysiological properties which may differ significantly among different compounds and also between isolated tissues in intact animals and man. As a class they do not increase the effective refractory period of the atria, ventricle, His-Purkinje fibres or the accessory pathways in the heart. The dominant effect is slowing of conduction in the AV node with the prolongation of the AV nodal refractory period. The most marked changes are produced by verapamil, the least with nifedipine which is devoid of antiarrhythmic actions. Verapamil and its congeners as well as diltiazem terminate paroxysmal supraventricular tachycardia and slow the ventricular response in atrial flutter and fibrillation. They are also of prophylactic value in preventing recurrences of paroxysmal supraventricular tachycardia and controlling the ventricular response in atrial flutter and fibrillation during long term oral therapy. Their value in ventricular arrhythmias is uncertain but they are unlikely to be effective except in those complicating coronary artery spasms. The relative merits and potencies of various calcium antagonists in different arrhythmias need further studies.
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PMID:Calcium antagonists. Clinical use in the treatment of arrhythmias. 633 97

Renal function and renin release were studied in anesthetized, uninephrectomized dogs during intrarenal infusions of the calcium influx blockers, verapamil and nifedipine. Verapamil increased renal blood flow by 20% (p less than 0.05) but did not alter glomerular filtration rate. Verapamil produced five-to-seven fold increases in urine flow and the rates of excretion of sodium and chloride (p less than 0.01). Significant increases in the rates of excretion of potassium, calcium and magnesium were also observed. Despite its striking effects on renal function, verapamil, in nonhypotensive doses, failed to alter renin secretion. Intrarenal infusion of nifedipine had no consistent effect on renal blood flow or the rate of glomerular filtration but increased urine flow and the rates of excretion of sodium and chloride by more than three fold (p less than 0.01). Nonhypotensive doses of nifedipine had no significant effect on renin release. In dogs with a denervated nonfiltering kidney, an intrarenal verapamil or nifedipine infusion did not produce a significant change in renin release. This study demonstrates a striking effect of calcium entry blockers on the reabsorption of sodium, chloride, and water by the renal tubules in intact dogs but renin release did not increase unless hypotension occurred.
Hypertension
PMID:Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs. 634 59

Verapamil and nifedipine are calcium-blocking agents that have a selective dilator effect on resistance vessels. Both drugs have been shown to lower arterial pressure when given in long-term therapy under conditions of a double-blind controlled trial. Both agents may be effective as sole therapy or when given in combination with a diuretic; nifedipine has been used successfully in conjunction with beta-adrenoceptor antagonist/diuretic combinations. Calcium-blocking agents do not evoke tolerance in long-term treatment; in contrast to other directly acting dilator drugs, they do not consistently lead to a rise in plasma renin activity and they induce little or no sodium retention. Calcium-blocking agents do not all share the same mechanism of action, and they vary considerably in their effect on the heart. These differences may be important in determining which compound is best suited for use in particular clinical situations.
Hypertension
PMID:Long-term efficacy of calcium antagonists in resistant hypertension. 634 71

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
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PMID:Update on calcium-channel blocking agents. 635 66


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