The safety and efficacy of once-daily nifedipine coat-core in combination with atenolol in hypertensive patients. Adalat CC Cooperative Study Group.

The efficacy and safety of once-daily nifedipine coat-core when added to a regimen of atenolol (ATN; 50 mg/day) were compared with ATN and placebo in 251 patients with essential hypertension in this 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Mean net reductions (ATN effect subtracted) in supine diastolic blood pressure at endpoint were 7.9 mmHg, 9.4 mmHg, and 9.9 mmHg at 30, 60, and 90 mg/day of nifedipine coat-core, respectively, and 4.1 mmHg on ATN+placebo. Beyond the first week of double-blind therapy, all reductions produced by nifedipine coat-core combined with ATN were statistically significant (P < 0.05) compared with ATN+placebo. On ambulatory blood pressure monitoring, trough-to-peak ratios of the change in diastolic blood pressure for the 30, 60, and 90 mg/day doses were 41%, 68%, and 78%, respectively. Adverse events were generally mild or moderate and most reflected the vasodilatory properties of nifedipine (eg, edema, headache). Nifedipine coat-core, when combined with ATN in patients not controlled by ATN alone, had significant antihypertensive activity for the entire 24-hour dosing interval and was well tolerated by the majority of patients in the study.

The efficacy and safety of once-daily nifedipine coat-core in the treatment of mild-to-moderate hypertension. Adalat CC Cooperative Study Group.

The efficacy and safety of once-daily nifedipine coat-core, a new, extended-release formulation, were examined in 245 patients with essential hypertension in this 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Mean net reductions in trough supine diastolic blood pressure at endpoint were 6.5 mmHg, 7.7 mmHg, and 11.7 mmHg at 30, 60, and 90 mg/day of nifedipine, respectively. All reductions were statistically significant, compared with placebo. Trough-to-peak ratios for supine diastolic blood pressure change following the 30, 60, and 90 mg/day doses were 49%, 67%, and 61%, respectively. Adverse events were generally mild or moderate, and most reflected the vasodilatory properties of the drug (eg, headache, edema). Reports of adverse events decreased as treatment progressed. The nifedipine coat-core tablet provided good control of blood pressure for the entire 24-hour dosing interval and was well tolerated by the majority of patients in the study.

1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth.

Recent studies from several laboratories have shown perturbations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism in hypertension. While these perturbations may exert their effect on blood pressure via their actions on calcium metabolism, it is possible that this vitamin D metabolite may have direct effects on vascular smooth muscle cell (VSMC) physiology. To examine this, we studied the effect of 1,25(OH)2D3 on VSMC growth and found that this substance suppressed VSMC [3H]thymidine uptake; furthermore, this vitamin D metabolite also suppressed the stimulatory effect of epidermal growth factor (EGF) on VSMC proliferation. The concomitant presence of this substance appeared to be required for its action on VSMC growth since cells pretreated with the vitamin D metabolite for up to 72 hours and then washed of the substance grew normally and responded to EGF. Studies were also done to determine if 1,25(OH)2D3 had any effect on the function of EGF receptors on VSMC. Experiments using Iodine-125-labeled EGF showed no differences in the binding of this ligand to VSMC, either untreated or treated with 1,25(OH)2D3, which indicates the effect of the vitamin D metabolite on VSMC growth (when exposed to EGF) was not mediated by an alteration of EGF receptor function. The results of these studies have implications for the pathogenesis of vascular diseases such as hypertension and atherosclerosis.

Combination therapy of hypertension with beta-adrenoceptor blockers and the calcium channel antagonist nitrendipine.

The combination of a beta-adrenoceptor-blocking drug with the dihydropyridine calcium channel antagonist, nitrendipine, has particular therapeutic advantages in the management of hypertension. The beta-blocker reduces any reflex increases in sympathetic nervous system and renin-angiotensin system activity that result from the vasodilating action of nitrendipine, whereas the latter drug reduces the peripheral effects of beta-blockade. At least three clinical studies have documented additional hypotensive effects when nitrendipine is used in combination with beta-blockers in the treatment of hypertension. This therapeutic combination is well tolerated, produces minimal alterations in clinical laboratory tests, and does not produce significant depression of atrioventricular conduction or left ventricular function.

Intravenous medroxalol stimulates prolactin secretion in normal and hypertensive subjects.

This study evaluated the effects of medroxalol on prolactin secretion. Twelve normal subjects received medroxalol, 1 mg/kg, intravenously and on a separate occasion, 5% dextrose in water. Integrated prolactin secretion during the 3 hours after medroxalol injection was significantly increased as compared with dextrose (P less than 0.001). Intravenous administration of medroxalol, 2 mg/kg, to 10 hypertensive subjects resulted in significant elevation of mean prolactin levels above basal levels at all time intervals measured from 30 to 240 minutes after injection. Oral medroxalol administration to 11 hypertensive subjects for up to 15 months did not alter mean prolactin levels. Medroxalol neither stimulated prolactin release nor decreased dopamine suppression of prolactin release from pituitary cell cultures. In conclusion, intravenous medroxalol stimulates prolactin secretion in both normal and hypertensive subjects. This effect is not likely mediated by a direct action of the drug on the pituitary but rather by an effect either within the central nervous system or of a drug metabolite.