Effects of renin-angiotensin system in mediating endothelin-induced renal vasoconstriction: therapeutic implications

Experiments were designed to determine whether angiotensin converting enzyme inhibition with quinaprilat can prevent endothelin-mediated decreases in renal blood flow and the glomerular filtration rate in the anesthetized dog.

To mimic the activation of the renal endothelin system that occurs in a number of cardiorenal disease states, endothelin was administered intrarenally in a group of mongrel dogs. Quinaprilat, the major active metabolite of quinapril, was infused in a separate group. One kidney (group 1) or both kidneys (group 2) were exposed in order to measure renal blood flow by an electromagnetic flow probe. Mean arterial blood pressure was measured through a catheter in a femoral vein. Blood samples were taken to determine plasma renin activity. Urine was collected.

The infusion of endothelin decreased renal blood flow and the glomerular filtration rate and increased 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 renal vascular responses.

These studies provide further evidence of the importance of the renal renin-angiotensin system in mediating the renal vasoconstrictor actions of endothelin and indicate the therapeutic potential for quinapril in opposing the actions of endothelin in states of excessive endothelin activation.