Increased Vascular Contractility and Oxidative Stress in beta(2)-Adrenoceptor Knockout Mice: The Role of NADPH Oxidase

Autor(es)

Davel, A. P. ^{[1, 2]} ; Ceravolo, G. S. ^[3] ; Wenceslau, C. F. ^[1] ; Carvalho, M. H. C. ^[3] ; Brum, P. C. ^[4] ; Rossoni, L. V. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

^[2] State Univ Campinas UNICAMP, Inst Biol, Dept Anat Cellular Biol Physiol & Biophys, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Phys Educ & Sport, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF VASCULAR RESEARCH; v. 49, n. 4, p. 342-352, 2012.
• Citações Web of Science: 17

Resumo

Background/Aims: beta(2)-adrenoceptor (beta(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal beta(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional beta(2)-AR (beta 2KO), focusing on the role of NO and superoxide anion. Methods and Results: Isolated thoracic aortas from beta 2KO and wild-type mice (WT) were studied. beta 2KO 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 beta 2KO and WT mice. Basal NO availability was reduced in aortas from beta 2KO mice. Incubation of beta 2KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. beta 2KO 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 beta 2KO aortas. Conclusions: The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of beta 2KO mice. This study extends the knowledge of the relevance of the endogenous activity of beta(2)-AR to the maintenance of the vascular physiology. Copyright (C) 2012 S. Karger AG, Basel (AU)

• Processo FAPESP: 07/58853-8 - Papel dos receptores beta1-, beta2- e beta3-adrenergicos nas alterações de função vascular e síntese de citocinas pró-inflamatórias induzidas pelo tratamento com isoproterenol em camundongos
• Beneficiário: Luciana Venturini Rossoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular