AT(1) receptor inhibition blunts angiotensin II-stimulated nitric oxide release in renal arteries

Nitric oxide (NO) is known to modulate the vascular effects of angiotensin II (AngII) in the kidney. To investigate the effect of AngII on NO release, a new technique was used that employs an NO-sensitive microelectrode to me asure NO release from the vascular endothelium of perfused renal resistance arteries (tertiary branches of the renal artery or primary arcuate arterie s) in vitro. The vessels were microdissected from isolated perfused rat kid neys, cannulated, and perfused at constant flow and pressure with Krebs-Rin ger bicarbonate solution. The electrode was placed inside the glass collect ion cannula to measure vessel effluent NO concentration. Addition of AngII to the perfusate stimulated NO release in a dose-dependent manner; 0.1, 10, and 1000 nM AngII increased NO oxidation current by 85 +/- 18 pA (n = 11), 148 +/- 22 pA (n = 11), and 193 +/- 29 pA (n = 11), respectively. These cu rrents correspond to changes in effluent NO concentration of 3.4 +/- 0.5, 6 .1 +/- 1.1 and 8.2 +/- 1.3 nM, respectively. The presence or 0.1 mM N-G-nit ro-L-arginine methyl ester in the perfusate significantly reduced the respo nse to 10 nM AngII by 90.5 +/- 3.4%, (n = 5). Neither losartan (1 mu M) nor candesartan (1 nM) significantly affected basal NO production, but both of these AT(1)-receptor blockers markedly blunted NO release in response to A ngII (10 nM): 77 +/- 6% inhibition with losartan (n = 8) and 63 +/- 9% with candesartan (n = 8). These results demonstrate that AngII stimulates NG-ni tro-L-arginine methyl ester-inhibitable NO release in isolated renal resist ance arteries. Because the response was significantly blunted by AT(1) rece ptor blockade, the findings suggest that endothelium-dependent modulation o f AngII-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT(1) receptor-dependent NO release.