The antihypertensive effect of captopril. Evidence for an influence of kinins.
The acute effect of the orally-active converting enzyme inhibitor, captopril, was compared to that of saralasin in 13 patients with various forms of hypertension on ad libitum sodium intake. A significant difference between the effects of the two drugs on mean arterial pressure (MAP) was found (-11 +/- 3 mm Hg with saralasin, -24 +/- 4.5 mm Hg after captopril). This difference was not correlated with control plasma renin activity (PRA). To determine the influence of the endogenous kallikrein-kinin system in the antihypertensive action of captopril, the effect of aprotinin (Apro), an inhibitor of kinin generation, on the MAP level achieved by captopril was assessed in five normal subjects and 15 patients with hypertension on ad libitum sodium intake. In normal subjects, captopril did not alter MAP, nor did Apro have any effect. In six patients with essential hypertension and normal PRA, MAP decreased by 5.5 +/- 2 mm Hg following captopril, and Apro did not modify this level. In nine patients with renovascular hypertension (RVH), MAP fell by 22 +/ 3 mm Hg after captopril administration, and Apro infusion induced a rise in MAP of 13 +/- 1.7 mm Hg. A positive correlation between log control PRA and the effect of aprotinin was obtained ( r = 0.63, p less than 0.005). Apro had no effect in two patients with RVH who experiences a large drop in MAP during salasin. These results suggest that endogenous kinins as well as other substances, the generation of which is inhibited by aprotinin, may participate to the antihypertensive effect of captopril in patients with angiotensin-dependent hypertension. The lack of an aprotinin effect on the MAP level achieved during saralasin infusion suggests that the influence of the kallikrein-kinin system is related to the effect of captopril rather than the fall in arterial pressure resulting from angiotensin blockade.
D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000502:physiology; D011392:Proline / Q000031:analogs & derivatives*; D012504:Saralasin / Q000627:therapeutic use
D007705:Kinins; D007611:Aprotinin; D011392:Proline; D002216:Captopril; D012504:Saralasin