Valsartan, a selective antagonist of angiotensin II at the AT1 receptor subtype, is an efficacious, orally active, blood pressure-lowering agent
used in hypertensive patients. Given that aminopeptidases (APs) play a major role
in the metabolism of local peptides involved in blood pressure control, studying them
helped us to understand cardiovascular control. We studied the effect of valsartan
on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney
in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP
and CysAP in renal cortex and medulla 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 soluble GluAP in the
medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity
was mainly downregulated following hypertension. Valsartan decreased soluble CysAP
activity in sham-operated, but not in hypertensive animals. The renal medulla showed
a significant valsartan-related decreased activity in clipped and non-clipped kidneys
of both sham-operated and hypertensive animals. These results suggest a functional
relationship between the AT1 receptor and vasopressin-degrading activity.
Key words:
Glutamyl Aminopeptidase - Cystinyl Aminopeptidase - Kidney - Renovascular Hypertension
- Valsartan
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M. Ramírez
Unit of Physiology
University of Jaén
Bldg. B3
23071, Jaén
Spain
Fax: + 34 (953) 012141
eMail: msanchez@ujaen.es
