Angiotensin II augments renal vasoconstriction via AT1 receptors in L-NAME-induced hypertensive rats.

Abstract

The renal renin angiotensin system modulates blood pressure via the action of angiotensin II at type 1 (AT1) and type 2 (AT2) angiotensin receptors. It has been proposed that there is an increased pressor response to angiotensin II (ANG II) in the hypertensive rat kidney. We determined the role of the AT1 receptor in L-NAME-induced hypertension. Male Wistar rats (250-300 g) were divided into control (tap water) and L-NAME (50 mg/kg/day/2 weeks) treated groups. Concentration-response curves to ANG II were constructed in isolated perfused kidneys and AT1 receptor expression was determined by Western blot in the renal cortex, medulla and papilla. ANG II evoked an increase in perfusion pressure in kidneys of both control and L-NAME-treated rats in a concentration-related manner. In L-NAME-treated rats, a greater maximal effect was observed compared to control rats (160 +/- 13 vs. 138 +/- 8 mmHg; p<0.05, respectively), suggesting that L-NAME promoted ANG II hypersensitivity. In both, control and L-NAME groups, the response to ANG II was blocked by the selective AT1 receptor antagonist losartan (1 x 10(-8) and 3.16 x 10(-8) M). AT1 receptor expression in kidney cortex, medulla and papilla did not show significant differences between groups. Our results demonstrate that AT1 receptor stimulation is related to renal vasculature hypersensitivity in L-NAME-induced hypertension.