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 less than 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 less than 0.05) following the highest isradipine dose, whereas plasma aldosterone was unmodified. Isradipine resulted in a statistically significant rise (p less than 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.
Rupoli
L
L
Istituto di Clinica Medica Generale e Terapia Medica, Università di Milano, Italy.
Fruscio
M
M
Gradnik
R
R
Chianca
R
R
Leonetti
G
G
Zanchetti
A
A
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017275:Isradipine; D007668:Kidney / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects; D010919:Placebos; D011725:Pyridines / Q000008:administration & dosage*; D011897:Random Allocation; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010919:Placebos; D011725:Pyridines; D012964:Sodium; D017275:Isradipine