Effect of SA-446, an Angiotensin-Converting Enzyme Inhibitor, on Renal Function in Anesthetized Dogs

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Abstract
I.v. infusion of SA-446 (1 mg/min) decreased systemic blood pressure and increased renal blood flow in anesthetized dogs. These changes were accompanied by a slight natriuretic response. During the infusion of this dose of SA-446, the pressor response to angiotensin I was abolished and the depressor response to bradykinin was markedly potentiated. Administration of indomethacin (13 mg/kg i.v.) suppressed natriuresis and, to some extent, the renal vasodilation caused by SA-446. Before and after administration of SA-446, 4 arachidonate metabolites, prostaglandin E2, prostaglandin F2.alpha., 6-keto-prostaglandin F1.alpha. and thromboxane B2, were determined in plasma and urine by radioimmunoassay. There were no remarkable changes in levels of prostaglandins and thromboxane B2 in arterial and renal venous plasma. The urinary excretion of the metabolites varied little, but thromboxane B2 excretion did significantly decrease. Thus, reduction in the biosynthesis of thromboxane B2 in the kidney may relate to the effects of SA-446 on renal hemodynamics and urine formation.