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Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in L-NAME-induced hypertensive rats.
Eur J Pharmacol. 2005 Jun 15; 516(3):253-9.EJ

Abstract

Male Sprague-Dawley rats given N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 8 weeks showed: (1) a clear-cut increase in systolic blood pressure; (2) a consistent decrease of endothelial-cell nitric oxide synthase (eNOS) gene expression in aortic tissue; (3) a marked reduction of plasma nitrite/nitrate concentrations; (4) a reduction of the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) on norepinephrine-precontracted aortic rings (reduction by 48+/-5%); (5) a marked decrease (-58%) of the basal release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings. In L-NAME-treated rats, administration in the last 4 weeks of either the angiotensin-converting enzyme (ACE) inhibitor enalapril (10 mg/kg/day in tap water) or the angiotensin AT(1)-receptor antagonist losartan (10 mg/kg/day in tap water) decreased systolic blood pressure levels, completely restored eNOS mRNA levels in aortic tissue and plasma nitrite/nitrate levels, and allowed a consistent recovery of both the relaxant activity of acetylcholine and the generation of 6-keto-PGF1alpha. Coadministration of icatibant, a bradykinin B(2)-receptor antagonist (200 microg/kg/day), with enalapril blunted the stimulatory effect of the ACE inhibitor on eNOS mRNA expression, circulating levels of nitrite/nitrate, the relaxant activity of ACh and the release of 6-keto-PGF1alpha in L-NAME-treated rats. The generation of 6-keto-PGF1alpha from aortic rings was also decreased in rats coadministered icatibant with losartan. These findings indicate that (1) the ACE inhibitor enalapril and the angiotensin AT(1)-receptor blocker losartan are equally effective to reverse NAME-induced endothelial dysfunction; (2) the beneficial effect of enalapril on the endothelial vasodilator function in L-NAME-treated rats is mediated by bradykinin B(2)-receptor activation; and (3) the enhanced endothelial generation of prostacyclin induced by losartan in L-NAME rats is also mediated by bradykinin B(2)-receptor activation.

Authors+Show Affiliations

Department of Pharmacology, Chemoterapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. vito.colonna@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15963975

Citation

De Gennaro Colonna, Vito, et al. "Angiotensin-converting Enzyme Inhibition and Angiotensin AT1-receptor Antagonism Equally Improve Endothelial Vasodilator Function in L-NAME-induced Hypertensive Rats." European Journal of Pharmacology, vol. 516, no. 3, 2005, pp. 253-9.
De Gennaro Colonna V, Rigamonti A, Fioretti S, et al. Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in L-NAME-induced hypertensive rats. Eur J Pharmacol. 2005;516(3):253-9.
De Gennaro Colonna, V., Rigamonti, A., Fioretti, S., Bonomo, S., Manfredi, B., Ferrario, P., Bianchi, M., Berti, F., Muller, E. E., & Rossoni, G. (2005). Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in L-NAME-induced hypertensive rats. European Journal of Pharmacology, 516(3), 253-9.
De Gennaro Colonna V, et al. Angiotensin-converting Enzyme Inhibition and Angiotensin AT1-receptor Antagonism Equally Improve Endothelial Vasodilator Function in L-NAME-induced Hypertensive Rats. Eur J Pharmacol. 2005 Jun 15;516(3):253-9. PubMed PMID: 15963975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in L-NAME-induced hypertensive rats. AU - De Gennaro Colonna,Vito, AU - Rigamonti,Antonello, AU - Fioretti,Simona, AU - Bonomo,Sara, AU - Manfredi,Barbara, AU - Ferrario,Paolo, AU - Bianchi,Mauro, AU - Berti,Ferruccio, AU - Muller,Eugenio E, AU - Rossoni,Giuseppe, PY - 2004/07/01/received PY - 2005/01/27/revised PY - 2005/02/02/accepted PY - 2005/6/21/pubmed PY - 2005/8/30/medline PY - 2005/6/21/entrez SP - 253 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 516 IS - 3 N2 - Male Sprague-Dawley rats given N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 8 weeks showed: (1) a clear-cut increase in systolic blood pressure; (2) a consistent decrease of endothelial-cell nitric oxide synthase (eNOS) gene expression in aortic tissue; (3) a marked reduction of plasma nitrite/nitrate concentrations; (4) a reduction of the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) on norepinephrine-precontracted aortic rings (reduction by 48+/-5%); (5) a marked decrease (-58%) of the basal release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings. In L-NAME-treated rats, administration in the last 4 weeks of either the angiotensin-converting enzyme (ACE) inhibitor enalapril (10 mg/kg/day in tap water) or the angiotensin AT(1)-receptor antagonist losartan (10 mg/kg/day in tap water) decreased systolic blood pressure levels, completely restored eNOS mRNA levels in aortic tissue and plasma nitrite/nitrate levels, and allowed a consistent recovery of both the relaxant activity of acetylcholine and the generation of 6-keto-PGF1alpha. Coadministration of icatibant, a bradykinin B(2)-receptor antagonist (200 microg/kg/day), with enalapril blunted the stimulatory effect of the ACE inhibitor on eNOS mRNA expression, circulating levels of nitrite/nitrate, the relaxant activity of ACh and the release of 6-keto-PGF1alpha in L-NAME-treated rats. The generation of 6-keto-PGF1alpha from aortic rings was also decreased in rats coadministered icatibant with losartan. These findings indicate that (1) the ACE inhibitor enalapril and the angiotensin AT(1)-receptor blocker losartan are equally effective to reverse NAME-induced endothelial dysfunction; (2) the beneficial effect of enalapril on the endothelial vasodilator function in L-NAME-treated rats is mediated by bradykinin B(2)-receptor activation; and (3) the enhanced endothelial generation of prostacyclin induced by losartan in L-NAME rats is also mediated by bradykinin B(2)-receptor activation. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15963975/Angiotensin_converting_enzyme_inhibition_and_angiotensin_AT1_receptor_antagonism_equally_improve_endothelial_vasodilator_function_in_L_NAME_induced_hypertensive_rats_ DB - PRIME DP - Unbound Medicine ER -