Studies on the natriuretic effect of nifedipine in hypertensive patients: increase in levels of plasma atrial natriuretic factor without participation of the renal kallikrein-kinin system.
We studied two groups of hypertensive patients in order to ascertain whether the acute natriuretic effect of nifedipine is mediated by humoral factors such as renal kallikrein or atrial natriuretic factor (ANF). First, 17 patients with mild to moderate essential hypertension maintained on a 130-mmol/day diet, received either nifedipine (10 mg orally) or placebo during a 6-h infusion of the kallikrein inhibitor aprotinin (2 x 10(6) KIU) or saline as control. Aprotinin, while significantly reducing urinary kallikrein activity, did not interfere with the acute effects of nifedipine on blood pressure, heart rate, urinary volume, urinary Na+ and creatinine clearance. In another group of eight patients on a constant daily Na+ intake of 130 mmol and in the supine position, placebo or nifedipine (10 mg sublingually) were administered, and blood pressure, heart rate, plasma renin activity, plasma aldosterone and plasma ANF, urinary Na+, urine volume and creatinine clearance, were monitored for 2 h. While placebo did not induce changes in any of the above parameters, nifedipine administration induced a significant decrease in blood pressure and increase in urinary Na+, urine volume and creatinine clearance, and a significant rise in ANF levels, from 19.4 +/- 2.8 pg/ml to a maximum of 23.9 +/- 2.5 and 24.1 +/- 2.2 pg/ml (P less than 0.05) at 60 and 90 min, respectively. In conclusion, our data do not support a role for renal kallikrein as a humoral mediator of the natriuretic effect of calcium antagonists, but do not exclude the possibility that ANF might participate in the nifedipine-induced increase in sodium and water excretion.
D000328:Adult; D007611:Aprotinin / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004341:Drug Evaluation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007610:Kallikreins / Q000652:urine*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007705:Kinins / Q000652:urine*; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D012964:Sodium / Q000652:urine
D007705:Kinins; D009320:Atrial Natriuretic Factor; D007611:Aprotinin; D012964:Sodium; D003404:Creatinine; D007610:Kallikreins; D009543:Nifedipine