Accentuated Vascular and Endocrine Response to Sq 20881 in Hypertension

Abstract

We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 μg per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5±1 mm Hg, P<0.05), and renal blood flow(+50±8 ml per 100g per minute), plasma renin activity (+2.3±0.6 ng per milliliter per hour), and angiotensin II (-11±3 pg per milliliter) more strikingly (P<0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 μg per kilogram; 30 μg per kilogram had an enhanced (P<0.01) effect on mean blood pressure (-11±2 mm Hg), renal blood flow (137±20 ml per 100 g per minute), and angiotensin II concentration (-29±12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4± 2.6 ng per milliliter, P<0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics. (N Engl J Med 297:184–188, 1977)