EFFECTS OF RENIN-ANGIOTENSIN SYSTEM IN MEDIATING ENDOTHELIN-INDUCED RENAL VASOCONSTRICTION - THERAPEUTIC IMPLICATIONS

Purpose: Experiments were designed to determine whether angiotensin co nverting enzyme inhibition with quinaprilat can prevent endothelin-med iated decreases in renal blood flow and the glomerular filtration rate in the anesthetized dog. Methods: To mimic the activation of the rena l endothelin system that occurs in a number of cardiorenal disease sta tes, endothelin was administered intrarenally in a group of mongrel do gs. Quinaprilat, the major active metabolite of quinapril, was infused in a separate group. One kidney (group 1) or both kidneys (group 2) w ere exposed in order to measure renal blood flow by an electromagnetic flow probe. Mean arterial blood pressure was measured through a cathe ter in a femoral vein. Blood samples were taken to determine plasma re nin activity. Urine was collected. Results: The infusion of endothelin decreased renal blood flow and the glomerular filtration rate and inc reased renal vascular resistance. These renal vascular responses were associated with increased plasma renin activity, indicating activation of the renal renin-angiotensin system. Quinaprilat attenuated the ren al vascular responses. Conclusion: These studies provide further evide nce of the importance of the renal renin-angiotensin system in mediati ng the renal vasoconstrictor actions of endothelin and indicate the th erapeutic potential for quinapril in opposing the actions of endotheli n in states of excessive endothelin activation.