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 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 AT(1) receptor and vasopressin-degrading activity.
Prieto
I
I
Unit of Physiology, University of Jaén, Bldg. B3, 23071, Jaén, Spain.
Martínez
J M
JM
Hermoso
F
F
Ramírez
M J
MJ
de Gasparo
M
M
Vargas
F
F
Alba
F
F
Ramírez
M
M
D000626:Aminopeptidases / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D043384:Glutamyl Aminopeptidase; D006978:Hypertension, Renovascular / Q000201:enzymology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010919:Placebos; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000068756:Valsartan
D000959:Antihypertensive Agents; D010919:Placebos; D013777:Tetrazoles; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000068756:Valsartan; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; D043384:Glutamyl Aminopeptidase; D014633:Valine