Effects of an orally active converting enzyme inhibitor (YS-980) on renal function in dogs.
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.
D015097:3-Mercaptopropionic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D007705:Kinins / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood / Q000378:metabolism; D013438:Sulfhydryl Compounds; D013722:Teprotide / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D053778:Thiazolidines; C019135:(4R)-3-((2S)-3-mercapto-2-methylpropanoyl)-4- thiazolidinecarboxylic acid; D007611:Aprotinin; D015097:3-Mercaptopropionic Acid; D013722:Teprotide; D007610:Kallikreins; D012083:Renin; D007213:Indomethacin