Antihypertensive Effect Of Verapamil Research Articles

Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy

Background The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended-release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. Methods: Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER-verapamil in patients with mid–stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil ( N = 273) or placebo ( N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. Results: Treatment with COER-verapamil caused significant reductions in 24-h and early-morning systolic and diastolic BP in all of the subpopulations as compared with placebo ( P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (−15.1 v −10.0 mm Hg; P < .001) and diastolic (−10.4 v −8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (−10.2 v −8.2 mm Hg; P < .05) and heart rate (−5.7 v −4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. Conclusions Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients.

Non-invasive haemodynamic study in hypertensive subjects after treatment with verapamil slow release

Aim of this study is to investigate the haemodynamic effects, after the short and long-term antihypertensive treatment. After a wash-out period and a placebo treatment period, 30 hypertensive patients received verapamil SR (slow release, 240 mg o.d.) for 30 days. A significant decrease in systolic and diastolic blood pressure was obtained already 4 h after the first administration of verapamil; it was more evident and persistent throughout the study. No significant changes of heart rate or PR interval in ECG were observed. A significant decrease in total vascular resistances, were observed. A significant decrease in total vascular resistances, both supine and upright, was evident already 4 h after the drug intake and observed throughout the study. The major effect was obtained after one month. No significant changes of cardiac output, cardiac index and stroke volume were recorded. Furthermore, plasma verapamil levels were measured to confirm that the haemodynamic effects are obtained by low drug concentrations. The present study provides evidence that the antihypertensive effect of verapamil, whose mechanism is the reduction of total vascular resistances, is progressive, long acting and achieved by low plasma levels, when slow release formulation is considered.

Verapamil-induced natriuretic and diuretic effects: dependency on sodium intake.

The influence of dietary sodium on the antihypertensive effects of verapamil and on components of sodium, water, and calcium metabolism was studied in nine white patients 50 to 65 years old with normal renin hypertension. Diets consisting of 109 and 259 mEq Na were given for 5 days each before the study drug was given. On days 4 and 9, intravenous verapamil (0.075 mg/kg) and oral verapamil (80 mg) were given, followed by 80 mg at 8-hour intervals for three doses. On days 1, 4, 5, 9, and 10, serum and urine electrolytes, osmolality (urine [Uosm], serum [Sosm], and osmolar clearance [Cosm]), calcium plasma renin activity (PRA), and levels of serum aldosterone, 1,25-hydroxyvitamin D, serum ionized calcium, parathyroid hormone, atrial natriuretic hormone (atriopeptin), and erythrocyte calcium and electrolytes were measured. On days 5 and 10, serial plasma samples for measurement of verapamil and norverapamil levels were drawn immediately after the last oral dose of verapamil. After verapamil, Uosm and Cosm decreased during both 109 and 259 mEq sodium diets (Uosm, p less than 0.025; Cosm, p less than 0.01 and p less than 0.025, respectively), but free water clearance increased during each diet (p less than 0.01). Urine volume and sodium excretion increased with the 259 mEq sodium diet (p less than 0.025 and p less than 0.01, respectively). There were no significant changes in measured values of components of calcium metabolism with either diet or after verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockade with Verapamil: Effects on Blood Pressure, Renal, and Myocardial Adrenergic, Cholinergic, and Calcium Channel Receptors in Inbred Dahl Hypertension-Sensitive (S/JR) and Hypertension-Resistant (R/JR) Rats

Verapamil HCl was chronically administered to inbred Dahl S/JR and R/JR rats maintained on a diet containing 8.0% NaCl (w/w) and the effects on blood pressure (BP) and heart rate (HR) were investigated. Treatment over a 4-week period via implanted miniosmotic pumps attenuated but did not prevent the development of salt-induced hypertension (HT) in the S/JR rat. Elevated HR, possibly reflexive in origin, was observed in S/JR rats that received verapamil but not in similarly treated R/JR rats. Although verapamil retarded the development of HT in S/JR rats, BP rose to moderately hypertensive levels, and the ventricle/body weight ratio was elevated by the termination of the study. The effect of verapamil on the density and affinity of alpha 1-, alpha 2-, and beta-adrenergic, muscarinic cholinergic, and calcium channel receptors in renal and ventricular membranes was also assessed. The density of renal and ventricular alpha 1- and beta-adrenoceptors was not affected by chronic drug treatment. The density of renal alpha 2- and beta-adrenoceptors was greater in the S/JR strain than in the R/JR strain, regardless of the treatment. The density of muscarinic cholinergic and calcium channel receptors in the ventricle was not affected by the treatment. The results of this study suggest that the long-term antihypertensive effects of verapamil in the S/JR rat do not involve an alteration in the binding characteristics of adrenergic, cholinergic, or calcium channel receptor sites in ventricular and renal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Study on Antihypertensive Effect of Verapamil

Clinical Study on Antihypertensive Effect of Verapamil

Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats.

In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers.

Effects of Verapamil and Aspirin on Experimental Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats

Rats made hypoxic by confinement in hypoxic cages for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Treatment with Verapamil or aspirin reduced both chronic hypoxic pulmonary hypertension and the hypertrophy of the right ventricle. The antihypertensive effect of Verapamil is explained by the involvement of the transmembrane calcium flux in pulmonary vascular smooth muscle in the hypoxic vasoconstrictory response. Part of the antihypertensive effect of inhibition of prostaglandin synthesis is attributed to a decrease in packed cell volume produced in hypoxic, aspirin treated rats.