Comparison of different drug interference with the renin-angiotensin system

The hypotensive effects of inhibitors of renin or converting-enzyme (CE) were compared in normotensive sodium-depleted marmosets. Renin was inhibited by an antiserum or a monoclonal antibody against human kidney renin or by peptidic renin inhibitors. The fall in blood pressure after the administration of renin antibodies or inhibitors was accompanied by complete inhibition of plasma renin activity. Antiserum and monoclonal antibody induced a hypotensive response of similar magnitude as peptidic renin inhibitors but had a longer duration of action. Teprotide was used as a CE-inhibitor. Inhibition of renin or CE lowered blood pressure but did not affect heart rate. The magnitude of the hypotensive effect was comparable after renin- or CE-inhibition and depended on the pretreatment plasma renin activity. Inhibition of renin prevented the hypotensive response to inhibition of CE and vice versa. The results of these comparative studies suggest that, in states of sodium depletion, the acute hypotensive effects of renin- or CE-inhibitors are entirely due to their interference with the renin-angiotensin system.