Cardiovascular and renal effects of single administration of three different doses of isradipine in hypertensive patients: Dose-response curves of the different effects

The antihypertensive, humoral, and renal effects of acute single oral administration of placebo and isradipine, a new dihydropyridine calcium antagonist, at doses of 2.5 mg, 5.0 mg, and 7.5 mg once daily were investigated in 11 patients with mild-to-moderate uncomplicated essential hypertension. The patients maintained a constant daily intake of 100 mmol of sodium and 40 mmol of potassium. Placebo and isradipine were randomly administered to each patient, according to a Latin-square design, at intervals of at least 48 hours. The antihypertensive effect was dose-dependent and peaked at two hours after oral administration; changes at the lowest dose were already statistically significant (p < 0.01). Increases in heart rate were mild and similar with all isradipine doses. Glomerular filtration rate and renal plasma flow showed a trend towards a dose-dependent rise; plasma renin activity was statistically increased (p < 0.05) following the highest isradipine dose, whereas plasma aldosterone was unmodified. Isradipine resulted in a statistically significant rise (p <0.05) in sodium excretion and urine volume, which was similar with all active doses. In conclusion, the antihypertensive efficacy of isradipine is dose-dependent, whereas the natriuretic and diuretic effects are already at maximum following 2.5 mg per day, the lowest dose in this study.