Acute restraint stress increases carotid reactivity in type-I diabetic rats by enhancing Nox4/NADPH oxidase functionality

Autor(es)

Moreira, Josimar D. ^[1] ; Pernomian, Larissa ^[2] ; Gomes, Mayara S. ^[3] ; Pernomian, Laena ^[4] ; Moreira, Rafael P. ^[3] ; do Prado, Alejandro F. ^[4] ; da Silva, Carlos H. T. P. ^[2] ; de Oliveira, Ana M. ^[3]

Afiliação do(s) autor(es)

^[1] Fed Univ Minas Gerais UFMG, Fac Pharm, Dept Clin & Toxicol Anal, Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto FCFRP, Dept Pharmaceut Sci, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, FCFRP, Dept Chem & Phys, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto FMRP, Dept Pharmacol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 765, p. 503-516, OCT 15 2015.
• Citações Web of Science: 10

Resumo

Hyperglycemia increases the generation of reactive oxygen species and affects systems that regulate the vascular tone including renin-angiotensin system. Stress could exacerbate intracellular oxidative stress during Diabetes upon the activation of angiotensin AT(1)/NADPH oxidase pathway, which contributes to the development of diabetic cardiovascular complications. For this study, type-I Diabetes was induced in Wistar rats by intraperitoneal injection of streptozotocin. 28 days after streptozotocin injection, the animals underwent to acute restraint stress for 3 h. Cumulative concentration-response curves for angiotensin II were obtained in carotid rings pre-treated or not with Nox or cyclooxygenase inhibitors. Nox1 or Nox4 expression and activity were assessed by Western blotting and lucigenin chemiluminescence, respectively. The role of Nox1 and Nox4 on reactive oxygen species generation was evaluated by flow cytometry and Amplex Red assays. Cyclooxygenases expression was assessed by real-time polymerase chain reaction. The contractile response evoked by angiotensin II was increased in diabetic rat carotid. Acute restraint stress increased this response in this vessel by mechanisms mediated by Nox4, whose local expression and activity in generating hydrogen peroxide are increased. The contractile hyperreactivity to angiotensin II in stressed diabetic rat carotid is also mediated by metabolites derived from cyclooxygenase-2, whose local expression is increased. Taken together, our findings suggest that acute restraint stress exacerbates the contractile hyperreactivity to angiotensin II in diabetic rat carotid by enhancing Nox4-driven generation of hydrogen peroxide, which evokes contractile tone by cyclooxygenases-dependent mechanisms. Finally, these findings highlight the harmful role played by acute stress in modulating diabetic vascular complications. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 14/17740-0 - Planejamento, desenvolvimento e avaliação farmacológica de novos antagonistas de receptores para hidrocarbonetos arila (AhR) candidatos a fármacos ateroprotetores
• Beneficiário: Larissa Pernomian
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/11205-7 - Modulação promovida pelo peptídeo natriurético tipo C (CNP) sobre a resposta contrátil induzida pela fenilefrina em aorta torácica e artérias mesentéricas de resistência isoladas de ratos submetidos ao choque séptico
• Beneficiário: Laena Pernomian
• Modalidade de apoio: Bolsas no Brasil - Doutorado