Clinical use of an orally acting converting enzyme inhibitor: Captopril

An orally Retire inhibitor of the angtotensin conrerting enzyme, SQ 14,225 or captopril, was administered to 14 normal rolnnteers to evaluate its efficacy in inhibiting the pressor response to exogenous angiotensin I. The degree of blockade was dose-related op to 10 mg of captopril. Increasing the dose further merely prolonged the duration of the blockade. Subsequently, 39 patients with various types of hypertension including some on maintenance bemodlalysis were treated chronically with captopril, i.e., 50 to 200 mg twice daily. The blood pressure (BP) reduction observed 1 hour following administration of the inhibitor was directly related to the baseline plasma renin activity (PRA) (r - 0.67, p < 0.001). Whenever blockade of the renin system alone did not lower BP to normal levels, additional sodium removal, e.g., by diuretics or ultraflltration, brought it under control. In eight additional untreated patients with essential hypertension, captopril induced an increase in renal plasma flow, which correlated significantly with PRA. Six normotensive patients with refractory congestive heart failure were also studied bemodynainically following an acute dose of captopril. Cardiac function improved while peripheral resistance decreased. These data suggest that the renin angiotensin system participates actively in maintaining the BP of patients with hypertension and the afterload in patients with congestive heart failure, and that blockade of this system represents an effective advance in therapeutics.