Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in l-NAME-induced hypertensive rats

摘要: Abstract Male Sprague–Dawley rats given N ω -nitro- l -arginine methyl ester ( -NAME) in drinking water for 8 weeks showed: (1) a clear-cut increase systolic blood pressure; (2) consistent decrease of endothelial-cell nitric oxide synthase (eNOS) gene expression aortic tissue; (3) marked reduction plasma nitrite/nitrate concentrations; (4) the relaxant activity acetylcholine (ACh, from 10 −10 to −4 M) on norepinephrine-precontracted rings (reduction by 48 ± 5%); (5) (−58%) basal release 6-keto-prostaglandin F1α (6-keto-PGF1α) rings. In -NAME-treated rats, administration last 4 either angiotensin-converting enzyme (ACE) inhibitor enalapril (10 mg/kg/day tap water) or angiotensin AT 1 -receptor antagonist losartan decreased pressure levels, completely restored eNOS mRNA levels tissue and allowed recovery both generation 6-keto-PGF1α. Coadministration icatibant, bradykinin B 2 (200 μg/kg/day), with blunted stimulatory effect ACE expression, circulating nitrite/nitrate, ACh 6-keto-PGF1α rats. The was also coadministered icatibant losartan. These findings indicate that blocker are equally effective reverse NAME-induced endothelial dysfunction; beneficial vasodilator function is mediated activation; enhanced prostacyclin induced -NAME activation.