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

Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelets, mediate platelet-induced vasoconstriction, which itself significantly contributes to coronary artery constriction in vivo. Platelet aggregatory response to serotonin is modulated by disparate effects of lipoprotein fractions. This corresponds to the recognized differences in degree of atherogenicity of low- (LDL) and high-density lipoprotein (HDL). Amplification of serotonin-induced platelet aggregation by LDL and its inhibition by HDL support the hypothesis that 5-HT-mediated effects represent a mechanism clinically relevant to both chronic progression of atherosclerosis (particularly at sites of vascular injury and atherosclerotic plaques) and acute thrombotic events. Calcium antagonists differ in their platelet-inhibition potency, including their effects on platelet response to 5-HT and LDL. Verapamil and isradipine inhibit platelet aggregation induced by 5-HT at therapeutic concentrations. Isradipine also inhibits the amplifying effect of LDL on 5-HT-induced aggregation. These platelet effects of calcium antagonists appear to be neither group- nor class-specific but, rather, drug-specific.
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PMID:Platelet activation by low-density lipoprotein and serotonin: effects of calcium antagonists. 137 30

In the present study, we describe the effects of Ca2+ channel antagonist (verapamil) on [3H]acetylcholine (ACh) release in the central nervous system of spontaneously hypertensive rats (SHR). The electrically stimulated release of [3H]ACh from striatal slices was not different between SHR and normotensive Wistar Kyoto (WKY) rats. Verapamil inhibited electrically stimulated [3H]ACh release in a dose-related fashion. The inhibitory effect of verapamil was significantly greater in SHR than in WKY rats. These results suggest that the Ca2+ sensitivity of central cholinergic neurons might be enhanced in SHR, which could attribute, at least partially, to the pathogenesis of hypertension.
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PMID:Effects of verapamil on [3H]acetylcholine release in the striatum of spontaneously hypertensive rats. 139 17

Abnormalities in sodium homeostasis and in atrial natriuretic peptide (ANP) behavior could play a role in determining and accelerating the development of glomerular hypertension, hypertension, and microalbuminuria in insulin-dependent diabetes. The aim of the present study was to investigate in 32 hypertensive insulin-dependent diabetic patients (HD) with an altered albumin excretion rate the natriuretic response and ANP release to saline load (2 mmol/kg 90 min, and the effects angiotensin converting enzyme inhibitor therapy 2.5 to 5.0 mg cilazapril, once daily), and calcium antagonists (sustained release verapamil: 120 to 240 mg Isoptin Press, once daily, and long acting nifedipine: 20 to 40 mg Adalat AR, twice daily) on sodium homeostasis and albumin excretion rate. Eight normal subjects matched for sex, age, and weight served as controls. The 32 HD patients showed a blunted response in ANP release and sodium excretion during saline infusion in comparison with controls. The cilazapril and verapamil treatments were tested in 16 of the 32 HD patients and were both effective in ameliorating natriuretic and ANP response to saline load and in decreasing albumin excretion rate. The combined cilazapril and verapamil treatment further improved both these parameters in these patients, although blood pressure levels were comparable. The other 16 HD patients underwent sequential verapamil and nifedipine treatment. Verapamil was more effective than nifedipine in improving natriuresis and ANP release to saline load and in lowering the albumin excretion rate. The results of the present study demonstrate that sodium homeostasis and ANP release are altered in hypertensive nephropathic patients, and both cilazapril and verapamil are more effective than nifedipine in ameliorating natriuresis, ANP release, and albumin excretion rate.
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PMID:Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients. 145 87

In this double-blind, parallel, multicenter study, sustained-release (SR) preparations of 2 calcium antagonists, nicardipine and verapamil, were compared for the treatment of mild to moderate systemic hypertension. Two hundred eighteen patients with supine diastolic blood pressures (BP) 95 to 114 mm Hg were randomly assigned to receive nicardipine-SR 45 mg twice daily (n = 73), nicardipine-SR 60 mg twice daily (n = 73) or verapamil-SR 240 mg once daily in the morning (n = 72). All 3 regimens significantly reduced supine and sitting systolic and diastolic BPs compared with baseline values (p < 0.005). The efficacy of drugs became apparent after 2 weeks of therapy, and was sustained throughout the 12-week study. Reductions in sitting diastolic BP and supine and sitting systolic BPs were statistically greater with nicardipine-SR 60 mg twice daily compared with verapamil, and nicardipine-SR 45 mg twice daily was equivalent to verapamil. Asthenia and constipation occurred more frequently in patients treated with verapamil (9.7 and 11.1%, respectively, compared with 6.8 and 4.1% in either nicardipine group). Adverse events reported more frequently with nicardipine were headache (17.8% with nicardipine-SR 60 mg and 15.1% with nicardipine-SR 45 mg vs 13.9% with verapamil) and edema (15.1% in the nicardipine-SR 60 mg group, 8.2% with nicardipine-SR 45 mg vs 4.2% with verapamil). Verapamil, but not nicardipine, produced significant reductions in heart rate. SR preparations of calcium antagonists offer options for effective monotherapy of systemic hypertension. Side-effect profiles differ and may affect choice of therapy.
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PMID:Comparison of sustained-release formulations of nicardipine and verapamil for mild to moderate systemic hypertension. 146 25

Vasodilators (verapamil, nifedipine, and prazosin) versus hypothiazide and clofelin were studied for their effects on resting and exercise blood levels of catecholamines in 58 patients with moderate arterial hypertension. Clofelin decreased norepinephrine levels, whereas hypothiazide increased it at rest and during exercise test. The most marked effect on norepinephrine levels was produced by nifedipine, then prazosin, particularly in patients with initially enhanced total peripheral vascular resistance. Verapamil failed to substantially affect norepinephrine levels. Due to the fact that the elevated levels of norepinephrine may have a negative action, it is suggested that antiadrenergic agents should be supplemented to a long-term therapy with nifedipine or prazosin.
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PMID:[Vasodilators and the catecholamine content of the blood plasma in patients with the moderate form of hypertension]. 148 68

This paper describes the results of a series of experiments in pithed rat, infused with angiotensin II, in order to characterize better vascular selectivity of lacidipine in comparison with other calcium entry blockers, namely amlodipine, verapamil and diltiazem. Lacidipine induced dose-related decreases in blood pressure (ED25% for mean blood pressure = 6 micrograms kg-1) with the appearance of second-degree A-V blocks at 300 micrograms kg-1. A slight decrease in contractile index (CI) was detected only at the highest dose used, 300 micrograms kg-1. The other dihydropyridine, amlodipine, showed a lower degree of vasodilatory activity (ED25% = 330 micrograms kg-1), appearance of second-degree A-V blocks starting from 1,000 micrograms kg-1 and a pronounced decrease in CI at 3,000 micrograms kg-1. Verapamil and diltiazem produced dose-related decreases in blood pressure (ED25% = 32 and 175 micrograms kg-1, respectively) and appearance of second-degree A-V blocks at 300 and 1,000 micrograms kg-1, respectively. Pronounced decreases in CI were detected with verapamil whereas diltiazem induced a more specific negative chronotropic effect. In conclusion, these results confirmed the marked vascular selectivity of lacidipine and give further evidence that this drug may be a suitable agent for the treatment of hypertension.
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PMID:A comparative study on the vascular selectivity of lacidipine in the pithed rat. 157 96

Verapamil, the first calcium-channel blocker to be introduced for clinical use, is a major drug used for the treatment of systemic hypertension. During the past 10 years, the use of verapamil for hypertension has produced a considerable clinical database to support the efficacy and safety of the agent in many patients. Because of its short half-life, verapamil was originally administered 3 to 4 times daily. During the past decade, a sustained-release formulation of verapamil has been marketed in the US. This product allows for once-daily dosing up to 240 mg/d; however, when higher doses are needed, this sustained-release formulation should be administered twice daily. In addition, the medicine should be taken with food to avoid the high peak blood levels of verapamil, which appears to be related to the delivery system. A new pellet-filled capsule formulation of verapamil (Verelan, Lederle, Wayne, NJ and Wyeth-Ayerst, Philadelphia, PA) is available and provides controlled absorption, 24-hour blood pressure control, improved peak-to-trough plasma levels, and once-daily dosing regardless of dosage size. Prolonged-release verapamil can be taken without food.
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PMID:Sustained-release verapamil formulations for treating hypertension. 158 64

In a double-blind, crossover study, five white men with mild-to-moderate hypertension received placebo and fixed doses of atenolol, metoprolol, chlorthalidone, verapamil, and the combination of atenolol and chlorthalidone in a quasi-random order. Daily dosages were: atenolol, 100 mg; metoprolol, 200 mg; chlorthalidone, 50 mg; verapamil, 240 mg; and the same doses of atenolol and chlorthalidone in combination. Standard office and daytime ambulatory blood pressures were assessed at the end of each month-long trial. Atenolol, metoprolol, chlorthalidone, and verapamil controlled office blood pressure with similar reductions. Verapamil did not lower ambulatory blood pressure at this dose (which is lower than is now commonly used), but reductions in ambulatory blood pressure were similar for atenolol, metoprolol, and chlorthalidone. The combination of atenolol and chlorthalidone maintained blood pressure control more effectively than the single drug treatments in both office and ambulatory settings, and the combined hypotensive effects were additive. However, reductions in the office due to the combination appeared to overestimate hypotensive effectiveness in the ambulatory setting. This study suggests that the effectiveness of commonly prescribed antihypertensive regimens varies according to setting as well as drug, and that assessment of treatment effectiveness can be improved by automated ambulatory blood pressure monitoring.
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PMID:Effectiveness of antihypertensive medications in office and ambulatory settings: a placebo-controlled comparison of atenolol, metoprolol, chlorthalidone, verapamil, and an atenolol-chlorthalidone combination. 163 45

The calcium antagonist verapamil was intravenously infused after plasma volume expansion with dextran-70 in nine patients with severe gestational proteinuric hypertension. The hemodynamic response of these patients was monitored using a flow-directed pulmonary artery catheter. Verapamil produced a statistically significant reduction in mean arterial pressure and systemic vascular resistance without adversely affecting the cardiac output. The decrease in blood pressure was smooth and controlled and was associated with an insignificant increase in heart rate. There were no adverse fetal effects as evidenced by cardiotocographic monitoring. The apparent efficacy of verapamil in this study justifies further investigation.
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PMID:Hemodynamic changes associated with intravenous infusion of the calcium antagonist verapamil in the treatment of severe gestational proteinuric hypertension. 169 82

We studied the effects of ouabain and verapamil on endothelin-1(ET-1)-induced contraction of the mesenteric artery in prehypertensive spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. Rings of mesenteric artery of SHRs and WKY rats aged 4 weeks were superfused with physiological saline solution and isometric tension was measured. ET-1 (10(-9) or 10(-8) M)-induced contractions were significantly larger in WKY rats than in SHRs. ET-1 (10(-7) M)-induced contractions were not significantly different between SHRs and WKY rats. Verapamil markedly inhibited ET-1 (10(-7) M)-induced contractions both in SHRs and in WKY rats. Although the percent inhibition tended to be larger in SHRs than in WKY rats, the difference was not significant. Ouabain significantly increased ET-1 (10(-7) M)-induced contraction in the presence of verapamil both in SHRs and in WKY rats. The increase was significantly greater in SHRs than in WKY rats. As a result, ET-1 (10(-7) M)-induced contractions were significantly greater in SHRs than in WKY rats in the presence of verapamil and ouabain. These results suggest that in ET-1-induced arterial contraction, [Na+]i-mediated [Ca2+]i regulation such as the Na+/Ca2+ exchange system might be greater in SHRs than in WKY rats, and that this might be, at least in part, involved in the pathogenesis or maintenance of hypertension in SHRs.
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PMID:Effects of ouabain and verapamil on endothelin-1-induced contraction of mesenteric artery in young spontaneously hypertensive rats. 172 23


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