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

Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are "pressure-related," such as stroke. However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy. This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties. Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action. Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease. Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies. In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies. Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study. Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease.
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PMID:Anti-atherosclerotic and vasculoprotective actions of calcium antagonists. 225 66

Calcium antagonists are popular therapeutic agents in the treatment of systemic hypertension. Although these agents have similar antihypertensive efficacy, they have varied effects on left ventricular function at rest in hypertensive patients. The effect of different calcium antagonists on left ventricular function during exercise and on exercise performance in patients with hypertension, however, is less clear. Fifteen patients with essential hypertension (diastolic blood pressure = 95 to 110 mm Hg) were enrolled in a placebo-controlled, single-blinded crossover study comparing nifedipine with verapamil for rest/exercise heart rate and blood pressure, exercise performance, and rest/exercise left ventricular function. Each drug was titrated to achieve resting diastolic pressures less than 90 mm Hg. All patients underwent maximal exercise testing and rest/exercise gated radionuclide ventriculography at the end of 3-week placebo, nifedipine, and verapamil treatment periods. Both calcium antagonists significantly reduced blood pressure at rest and during exercise compared with placebo. Neither calcium antagonist altered resting heart rate; however, both verapamil and nifedipine significantly reduced heart rate at maximal exercise. Verapamil but not nifedipine impaired left ventricular peak emptying rate and left ventricular peak filling rate during exercise but not at rest. Neither verapamil nor nifedipine, however, significantly altered rest or exercise global left ventricular ejection fraction (LVEF) compared with placebo. There was a trend, however, for impairment in the LVEF response to exercise (delta LVEF) in the verapamil treatment group. Exercise capacity was not significantly altered by either calcium antagonist compared with placebo. Thus verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Verapamil but not nifedipine impairs left ventricular function during exercise in hypertensive patients. 230 6

The effects of caffeine on aortic smooth muscle contractility during hypertension were studied in SHR and WKY control rats. To compare the effects of Mg++ on vascular reactivity induced by caffeine 1.2 mM MgCl2 was either included or omitted from the Krebs solution bathing the aortic tissue. The role of alpha-adrenergic receptors and verapamil-sensitive Ca++ channels in eliciting caffeine induced contraction in aortic tissues was also examined in Sprague Dawley rats. We report that the aortic smooth muscle from SHR animal was less responsive than WKY aortic smooth muscle to 10 and 20 mM concentrations of caffeine. Caffeine induced a relaxation of aortic smooth muscle contracted with 60 mM KCl or 10(-7) M NE. However, the relaxation response was slower in SHR as compared to WKY rats. To assess the involvement of alpha-adrenergic receptors in caffeine induced aortic contractility alpha 1- and alpha 2-receptors were blocked with 10(-7) M prazosin and 10(-7) M yohimbine respectively. The caffeine induced aortic contractility did not seem to involve alpha-adrenergic receptors. A blockade of verapamil sensitive Ca++ channels with 10(-7) M verapamil failed to inhibit caffeine induced aortic contractility. These results indicate that caffeine involves release of Ca++ in vascular muscle, however, Ca++ is released from a site other than the one controlled by alpha-adrenergic receptors. Also, the Ca++ channels involved are other than the Verapamil sensitive Ca++ channels. Yet it is clear that if the aortic contractility is due to Ca++ release alone, then caffeine is a potent agent for Ca++ release in the aortic smooth muscle of rat. Additionally, the caffeine-sensitive mechanism for aortic smooth muscle contraction is impaired during hypertension.
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PMID:In vitro caffeine induced aortic smooth muscle reactivity in rat. 233 85

Hypertension is a serious side-effect of the clinical use of Cyclosporin A (CsA). One notion is that alterations of vascular reactivity contribute to this hypertension. In this study we used the isolated rat mesenteric vascular bed to test the specific hypothesis that CsA modifies vascular calcium regulation to potentiate vascular contractility. Mesenteric vessels from CsA-treated rats (10 mg/kg/day i.m. for 7 days) exhibited significantly greater vasoconstrictor responses to exogenous norepinephrine (NE) and potassium-induced depolarization than those of vehicle-treated animals. Similarly, in vitro CsA (8.3 X 10(-8) to 8.3 X 10(-6) M) augmented in a concentration-dependent manner both the sensitivity and the maximum response to NE and potassium. This effect of CsA on vasoconstriction was critically dependent on the presence of external calcium [( Ca++]o). The degree of vasoconstriction potentiation correlated significantly with the [Ca++]o which was used during exposure of the mesenteric bed to CsA. Reapplication of external calcium in the presence of CsA to "calcium-depleted" preparations increased significantly the amplitude of subsequent NE responses in a calcium-free medium. Thus, CsA-potentiated NE responses, once established, were not reversed by removing external calcium; however, attenuation occurred with the intracellular calcium antagonist dantrolene. Verapamil and nifedipine blocked potassium-elicited responses, but failed to prevent the CsA effect on NE-induced vasoconstriction. We conclude that CsA potentiation of vasoconstriction depends on extracellular calcium, and results from an enhanced transmembrane calcium transport. We speculate that CsA also increases the filling of intracellular stores of releasable calcium. These effects lead to greater calcium influx and greater intracellular calcium release upon stimulation.
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PMID:Mechanism of cyclosporin potentiation of vasoconstriction of the isolated rat mesenteric arterial bed: role of extracellular calcium. 239 12

Mg and verapamil have similar effects on the cardiovascular system. Both the agents have been successfully used for the treatment of hypertension and protection of the ischaemic myocardium. The exact mechanism of action of calcium blocking drugs including verapamil is unknown. It is proposed that verapamil stimulates the Mg-carrying transport system and Mg diffusion in the cell so that Mg influx is enhanced. This in turn causes suppression of the slow inward Ca current and fast inward Na current resulting into decreased transport of Ca and Na. Verapamil possibly also influences outward K and Mg currents and alter the shape and duration of the action potential. Since Mg ions maintain the structural and functional integrity of the cardiovascular system, therefore Mg mediated mechanisms of action for verapamil appears to be more logical.
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PMID:Is verapamil a better magnesium agonist rather than a calcium antagonist? A hypothesis? 244 62

The purpose of this study was to investigate the effects of the calcium channel blocker verapamil in the management of patients with both high blood pressure and orthostatic hypotension. Six hypertensive patients, aged 37-78 years, mean 60.8 +/- 3.2 years, four men and two women, with symptomatic orthostatic hypotension were included in this open study. Verapamil, 240 to 360 mg/day, decreased blood pressure and did not impair orthostatic hypotension with a mean follow-up of 6 months. Blood pressure and heart rate were, in lying and standing position, respectively, as follows: 177.5 +/- 5.9/99.1 +/- 9.9 mm Hg and 81.0 +/- 9.0 beats/min and 120.0 +/- 4.8/83.3 +/- 4.0 mm Hg and 91.0 +/- 9.5 beats/min before treatment; then, 155.8 +/- 5.5/89.1 +/- 4.2 mm Hg and 74.5 +/- 8.6 beats/min and 127.5 +/- 7.3/83.3 +/- 4 mm Hg and 83.0 +/- 9.1 beats/min after verapamil. In three patients with orthostatic hypotension successfully treated by the peripheral dopaminergic antagonist domperidone 60 mg/day, the subsequent introduction of verapamil 240 mg/day did not modify the standing-induced decrease in systolic blood pressure: 46.6 mm Hg under domperidone and 30.0 mm Hg under domperidone plus verapamil. Verapamil increased baroreflex sensitivity from 1.4 to 3.5 ms/mm in all patients. This preliminary study shows the interest of verapamil in the difficult management of hypertension with orthostatic hypotension. It is suggested that verapamil could increase the baroreflex sensitivity in patients with orthostatic hypotension.
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PMID:Hypertension with orthostatic hypotension: interest of verapamil. 245 8

From a hemodynamic point of view, the calcium antagonists represent an interesting way of treating hypertension, because they reduce total peripheral resistance without compromising cardiac output. Blood flow is also maintained during muscular exercise. Verapamil and diltiazem induce slight reduction in heart rate, but this is compensated by increase in stroke volume. Verapamil and diltiazem also prolong atrioventricular conduction time, in contrast to the dihydropyridines. Most clinical data are available for verapamil, diltiazem, and nifedipine. In patients with mild-to-moderate hypertension, these compounds seem as effective as diuretics and beta-blockers. They do not induce disturbances in glucose metabolism, serum uric acid, or serum potassium, and unwanted disturbances in blood lipids have not been described. The dihydropyridines may safely be combined with beta-blockers, but the combination of either verapamil or diltiazem with a beta-blocker should be avoided (because of the high risk of bradycardia). The calcium antagonists seem particularly useful in patients with the combination of hypertension and angina pectoris or peripheral vascular diseases or chronic obstructive lung diseases or diabetes. They are also effective in hypertensive crises. They may also be tried as a first line drug in patients with mild and moderate essential hypertension, particularly when diuretics or beta-blockers are contraindicated. Temporary side effects due to vasodilatation (headache, flushing, and palpitations) are seen frequently, particularly on the dihydropyridines. Edema is the most frequent serious side effect of the dihydropyridines, and constipation is most common with verapamil. At this point, few long-term data are available and it is not known whether the calcium antagonists will give better or worse results, with respect to morbidity and mortality, than the beta-blockers, diuretics, or other more recent antihypertensive agents.
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PMID:Clinical use of calcium antagonists in hypertension: update 1986. 245 35

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory blood pressure, casual blood pressure, plasma concentrations of angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, serum creatinine, plasma lipids and lipoproteins, and body weight were determined at the end of two consecutive 3-week periods; placebo was administered in the first period and verapamil sustained-release 240 mg was given in the second period. Verapamil reduced mean 24-h ambulatory blood pressure from 152/104 mm Hg (means) to 142/97 mm Hg. Blood pressure was reduced significantly during the daytime, in the evening, and in the early morning, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were determined in the hormones, serum creatinine, plasma lipids and lipoproteins, heart rate, or body weight. Atrial natriuretic peptide was correlated significantly with serum creatinine (p = 0.733, n = 14, p less than 0.01). We conclude that verapamil sustained-release 240 mg in one daily dose has a moderate blood-pressure-lowering effect in patients with chronic renal disease and hypertension without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increase in body weight, and without altering renal function and plasma lipids and lipoproteins. The positive correlation between atrial natriuretic peptide and serum creatinine may support the hypothesis that extracellular volume increases during progression of renal disease.
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PMID:Verapamil sustained-release in renal parenchymal hypertension: effect on blood pressure, kidney function, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, and lipoproteins. 247 77

In an open multicenter trial (uncontrolled study) in 4,247 patients (49.1% male, 50.9% female; aged 17-89 years) with mild, moderate, or severe hypertension, the antihypertensive efficacy and in particular the tolerability of verapamil slow-release (SR) 240 mg (Isoptin RR) were studied. The dosage of the drug was adjusted to the therapeutic response; in 88.7% of the patients it was titrated according to the study protocol: 63.2% received constantly one SR tablet throughout the 6-week treatment period; in 15.6% the dosage was increased to one and a half tablet after 2 weeks, and in 9.9% to one tablet b.i.d. after a further 2 weeks. Monotherapy with verapamil SR 240 mg normalized diastolic blood pressure (less than or equal to 90 mm Hg) in 90% of the patients with mild hypertension, 77% of those with moderate, and 61% of those with severe hypertension. It was evident that blood pressure reduction was more pronounced the higher the baseline value. Cardiac and extracardiac tolerability of verapamil SR 240 mg was good. Mean heart rate was slightly reduced, none of the patients developed a second- or third-degree atrioventricular block. Side effects were reported by 480 of the 4,247 patients (11.3%). As expected, constipation (4.03%) was the predominant adverse reaction, followed by dizziness (3.65%), headache (1.54%), and other (less than 1%). In 217 patients (5.1%) therapy was discontinued prematurely, in 139 (3.27%) because of side effects.
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PMID:Efficacy and safety of verapamil SR 240 mg in essential hypertension: results of a multicentric phase IV study. 247 86

The efficacy of verapamil, a calcium channel blocker in slow-release form, 240 mg once a day, was assessed in 1,412 ambulatory, mildly to moderately hypertensive patients. Blood pressure decreased from 171.82 +/- 17/103.55 +/- 6 mm Hg at week 0 to 157 +/- 15/93.6 +/- 8 mm Hg at 2 weeks (p less than 0.001) in 78% of patients. At week 12 there were 1,249 patients (88%) controlled with therapy, either with verapamil alone (950 patients, 67%) or plus additional diuretic (21%). Blood pressure showed a mean decrease of 24.6 mm Hg in systolic and 17.2 mm Hg in diastolic pressure at week 12. Heart rate decreased from 81.4 +/- 11 beats/min at week 0 to 75.69 +/- 8.5 beats/min at week 12 (p less than 0.05). There were no statistical differences in the effect on diastolic blood pressure between elderly (greater than 65 years) and nonelderly patients in the study, although the elderly showed higher baseline systolic pressure (178.27 +/- 17 mm Hg vs. 168.97 +/- 16 mm Hg, p less than 0.001) than did nonelderly patients. Verapamil therapy produced a similar effect on systolic pressure (p = NS) in younger patients (23.96 mm Hg decrement) and in the elderly (25.93 mm Hg decrement). The overall incidence of adverse reactions was 16.58%, accounting for 1.06% of patients' withdrawals. Constipation (5%) was the most common side effect. We conclude that slow-release verapamil, 240 mg once a day, is an effective therapeutic alternative in systemic hypertension, and must be included in the first step of antihypertensive therapy.
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PMID:Treatment of mild to moderate hypertension with verapamil slow-release in outpatients. Collaborative Group of the Spanish League for the Fight Against Hypertension. 247 87


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