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Type: Artigo de periódico
Title: Increased Vascular Contractility And Oxidative Stress In β₂-adrenoceptor Knockout Mice: The Role Of Nadph Oxidase.
Author: Davel, A P
Ceravolo, G S
Wenceslau, C F
Carvalho, M H C
Brum, P C
Rossoni, L V
Abstract: β(2)-adrenoceptor (β(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal β(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional β(2)-AR (β(2)KO), focusing on the role of NO and superoxide anion. Isolated thoracic aortas from β(2)KO and wild-type mice (WT) were studied. β(2)KO aortas exhibited an enhanced contractile response to phenylephrine compared to WT. Endothelial removal and L-NAME incubation increased phenylephrine-induced contraction, abolishing the differences between β(2)KO and WT mice. Basal NO availability was reduced in aortas from β(2)KO mice. Incubation of β(2)KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. β(2)KO aortas exhibited oxidative stress detected by enhanced dihydroethidium fluorescence, which was normalized by apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was enhanced in β(2)KO aortas. The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of β(2)KO mice. This study extends the knowledge of the relevance of the endogenous activity of β(2)-AR to the maintenance of the vascular physiology.
Subject: Acetophenones
Aorta, Thoracic
Endothelium, Vascular
Mice, Knockout
Nadph Oxidase
Nitric Oxide
Nitric Oxide Synthase Type Iii
Oxidative Stress
Receptors, Adrenergic, Beta-2
Citation: Journal Of Vascular Research. v. 49, n. 4, p. 342-52, 2012.
Rights: fechado
Identifier DOI: 10.1159/000337486
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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