Renal actions of the new angiotensin converting enzyme inhibitor CGS 16617

Abstract

Renal actions of the new angiotensin converting enzyme inhibitor CGS 16617 were evaluated in anesthetized dogs. Intravenous administration of 0.4 mg/kg CGS 16617 resulted in complete inhibition of the pressor response to 1 microgram angiotensin I (ANG I) for a 2 hr period. Over this period, i.v. injection of CGS 16617 significantly reduced mean arterial pressure (MAP) by 9 mmHg and significantly increased renal blood flow and glomerular filtration rate. Sodium and water excretion increased significantly following converting enzyme inhibition. Intravenous injection of CGS 16617 also markedly decreased urine osmolality and produced a highly significant increase in free water formation. Intravenous infusion of 0.5 microgram/kg per min saralasin also completely inhibited the pressor response produced by 1 microgram of ANG I. Except for the absence of a significant change in urinary osmolality, the changes in MAP and renal function produced by saralasin were essentially identical to those produced by CGS 16617. The results presented in this study demonstrate that the new converting enzyme inhibitor CGS 16617 has potent actions on renal function. The similarity of the changes in blood pressure and renal function produced by CGS 16617 to those of saralasin may suggest that the consequences of angiotensin converting enzyme inhibition in this model can largely be explained by inhibition of the renin-angiotensin system.