Effects of an orally active converting enzyme inhibitor (YS-980) on renal function in dogs

Abstract

The angiotensin converting enzyme inhibitor is a valuable pharmacological tool for studying the role of intrarenal humoral factors such as the renin-angiotensin and kallikrenin-kinin systems and prostaglandins as related to the regulation of renal function and the interrelation among them. An intrarenal infusion of such an inhibitor, YS-980 (thiazolidine carboxylic acid derivative), at a rate of 0.1 mg/min resulted in a significant fall in systemic arterial blood pressure and a significant increase in renal blood flow, urine flow, urinary excretion of sodium and renin release in anesthetized dogs. These renal effects evoked by YS-980 were abolished after the inhibition of kallikrein as induced by aprotinin (900 kallikrein inhibitory units per min). In addition, YS-980 given after the administration of indomethacin (5 mg/kg i.v.) had no effect on the renal hemodynamics and renin release except for the urinary excretion of sodium. These findings suggest that both the kallikrein-kinin system and prostaglandins contribute to the renal action and the vasodepressor effect of YS-980. It would appear that the intrarenal administration of this angiotensin converting enzyme inhibitor induced marked renal effects through activation of kinin and prostaglandins and that the relative contribution of the renin-angiotensin system is negligible in anesthetized dogs.