Effect of inhibition of peptidase activity on distribution of intrarenal blood flow.

Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion.