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.

Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats / V. De Gennaro Colonna, G. Rossoni, A. Rigamonti, S. Bonomo, B. Manfredi, F. Berti, E. Muller. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 450:1(2002 Aug 16), pp. 61-66. [10.1016/S0014-2999(02)02046-0]

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

V. De Gennaro Colonna;G. Rossoni;A. Rigamonti;B. Manfredi;
2002-08-16

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.
endothelial dysfunction; NO (nitric oxide); hypertension; angiotensin-converting enzyme inhibitor
Settore BIO/14 - Farmacologia
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/195959
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