Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats

Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor s ubtype, is an efficacious, orally active, blood pressure-lowering agent use d in hypertensive patients. Given that aminopeptidases (APs) play a major r ole in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied t he effect of valsartan on angiotensin II- (GluAP) and vasopressin(CysAP) de grading activities in the kidney in the rat model of renovascular hypertens ion, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and med ulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased sol uble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertensio n. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-rela ted decreased activity in clipped and non-clipped kidneys of both sham-oper ated and hypertensive animals. These results suggest a functional relations hip between the AT(1) receptor and vasopressin-degrading activity.