Hypotensive and natriuretic effects of nifedipine in essential hypertension. Role of renal kallikrein-kinin-prostaglandin and renin-angiotensin-aldosterone systems.
To assess the role of renal kallikrein-kinin-prostaglandin and renin-angiotensin-aldosterone systems in the diuretic and natriuretic actions of nifedipine, a calcium-channel blocker, 20 mg of nifedipine was administered orally to 15 patients with essential hypertension. Nifedipine promptly induced a hypotensive effect and an increase in pulse rate. Urine volume, urinary sodium excretion, and creatinine clearance were significantly increased after the administration of nifedipine by 63.5%, 48.5% and 12.4%, respectively. Urinary excretion of kallikrein and prostaglandin E were also significantly increased after the administration of nifedipine by 29.4% and 50.0%, respectively. The change in urinary kallikrein excretion was significantly correlated with that in urine volume (r = 0.70, p less than 0.01) or that in urinary sodium excretion (r = 0.86, p less than 0.01). In addition, the change in urinary prostaglandin E excretion was also significantly correlated with that in urine volume (r = 0.72, p less than 0.01) or that in urinary sodium excretion (r = 0.53, p less than 0.05). Plasma aldosterone concentration did not change despite of the marked increase in plasma renin activity, and plasma aldosterone concentration/plasma renin activity ratio decreased after the administration of nifedipine. These results suggest that the augmented renal kallikrein-kinin-prostaglandin system and the suppressed secretion of aldosterone may be associated with the diuretic and natiuretic action of nifedipine and may contribute to the reduction in blood pressure that is caused mainly by its vasodilatory action.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000652:urine; D007610:Kallikreins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D011458:Prostaglandins E / Q000652:urine*; D012084:Renin-Angiotensin System / Q000187:drug effects*
D011458:Prostaglandins E; D007610:Kallikreins; D009543:Nifedipine