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Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats.

Abstract：

:Endothelial dysfunction ensuing inhibition of nitric oxide synthase (NOS) was investigated in male Sprague-Dawley rats given N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 8 weeks. Age-matched rats served as controls. L-NAME-treated rats, as compared to control animals, showed: (1) a clear-cut increase in systolic blood pressure; (2) a consistent decrease of endothelial-cell NOS (eNOS) gene expression in aortic tissue; (3) a reduction of the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) on norepinephrine-precontracted aortic rings (reduction by 52+/-5%); (4) a marked decrease (-50%) of the basal release of 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) from aortic rings. In L-NAME-treated rats, administration in the last 2 weeks of either the angiotensin-converting enzyme inhibitor enalapril (1 mg/kg/day) or the cognate drug quinapril (1 mg/kg/day) decreased systolic blood pressure levels, completely restored eNOS mRNA levels in aortic tissue, and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF(1 alpha). No difference was present in the ability of the two angiotensin-converting enzyme inhibitors to reverse NAME-induced endothelial dysfunction. These findings indicate that L-NAME-induced hypertension in the rat relies on the marked impairment of the endothelial vasodilator function, with an ensuing contribution by a decreased production of prostacyclin by the endothelial cells. Angiotensin-converting enzyme inhibition by enalapril or quinapril was equally effective in improving endothelial vasodilator function, prostacyclin endothelial production and restoring aortic eNOS mRNA.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

De Gennaro Colonna V,Rossoni G,Rigamonti A,Bonomo S,Manfredi B,Berti F,Muller E

doi

10.1016/s0014-2999(02)02046-0

keywords:

subject

Has Abstract

pub_date

2002-08-16 00:00:00

pages

61-6

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014299902020460

journal_volume

450

pub_type

杂志文章

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