Effects of the oral converting enzyme inhibitor SQ 14225 in experimental high output failure

Abstract

The relation of the renin-angiotensin-aldosterone system to sodium retention was studied in dogs with an aortic-caval fistula and high output failure by administering orally the new converting enzyme inhibitor SQ 14225. The acute response to an initial oral dose of SQ 14225 (10 mg/kg) consisted in a fall in arterial pressure (BP) from 97 to 67 mmHg, plasma aldosterone concentration (PAC) from 21.7 to 11.3 ng/100 ml, creatinine clearance (CCr) from 89 to 44 ml/min, and filtration fraction (FF) from 39 to 18%, whereas plasma renin activity (PRA) increases from 12.7 to 36.1 ng angiotensin I.ml-1.h-1 and renal sodium excretion was unchanged. It is suggested that the marked fall in BP and CCr offset the drop in PAC and FF which favored a natriuresis. The daily responses to SQ 14225 for 3 days also showed a fall in BP and PAC but sodium excretion increased. In the animal with the best response, a striking natriuresis occurred. These findings demonstrate an important role for the renin-angiotensin-aldosterone system in experimental high output failure.