Antihypertensive and renal effects of captopril in relation to renin activity and bradykinin-induced vasodilation.
The effect of captopril on blood pressure and renal hemodynamics in relation to plasma renin activity (PRA) was assessed together with the vasodilator responses to brachial artery infusions of bradykinin (BK) and sodium nitroprusside (NP) before and after 4 wk of therapy with doses of up to 450 mg/day in patients with essential hypertension. The average blood pressure reduction of captopril was from 174.4/110.6 to 155.3/96.6 mm Hg (n = 12, P less than 0.001) without increases in heart rate or body weight. It was effective in the eight patients with normal renin, but showed little effect in the four with a low renin. There was a correlation between the changes in blood pressure after captopril and the pretreatment PRA (r = -0.82, P less than 0.01 for mean pressure). Brachial artery infusions of BK and NP induced dose-dependent rises in forearm blood flow (FBF), but this was not related to the captopril blood pressure-lowering effect. Repeat measurements during captopril therapy showed a shift to the left of the BK/FBF, but not of the NP/FBF, dose-response curve, indicating effective vascular kininase II inhibition. Captopril decreased renal vascular resistance. Our data are compatible with the view that captopril's antihypertensive action mainly involves blockade of the renin-angiotensin-aldosterone system and not cumulation of BK. The favorable effects on renal hemodynamics and the lack of tachycardia and volume retention after captopril make it a valuable drug for the treatment of hypertension.
D000328:Adult; D000959:Antihypertensive Agents; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D009599:Nitroprusside; D011392:Proline; D002216:Captopril; D001920:Bradykinin