Logotipo XV CONGRESSO BRASILEIRO DE ATEROSCLEROSE

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Departamento de Aterosclerose

Alameda Santos, 705 – 11º andar, Cerqueira Cesar/SP
(11) 3411-5531

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TRABALHOS APROVADOS > RESUMO

ACUTE STRESS INCREASES NOX4-DRIVEN GENERATION OF H2O2 AND ENOS ACTIVATION IN TYPE-I DIABETIC RAT CAROTID

Rafael Pires Moreira , Josimar Dornelas Moreira, Larissa Pernomian, Mayara Santos Gomes, Alejandro Ferraz do Prado, Ana Maria de Oliveira
Universidade Federal do Amapá - UNIFAP - Macapá - AP - Brasil, UFMG - Belo Horizonte - MG - Brasil, USP - Ribeirão Preto - SP - Brasil

Introduction: NADPH-oxidase is an important source of reactive oxygen species generated in hyperglycemia. Behavioral stress could exacerbate intracellular oxidative stress during Diabetes upon the activation of angiotensin AT1/NADPH-oxidase pathway and subsequently contribute to damage the vascular system. Methods: Type-I Diabetes was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration–response for angiotensin II (AngII) (10 pmol/l–1mmol/l) were obtained in endothelium intact (E+) or endothelium-denuded (E-) carotid rings from Diabetic rats that underwent to acute restraint stress for 3 h, in the presence of superoxide anion (O2-) scavenger (Tiron 100μmol/l), hydrogen peroxide (H2O2) scavenger (PEG-Catalase 250U/ml) or  endothelial nitric oxide synthase (eNOS) inhibitor (L-NNA, 100μmol/l) added 30 min prior to AngII. Peroxynitrite by 3-Nitrotirosine and eNOS expression and activity were assessed by Western blotting. The O2- and H2O2 levels were measured by flow cytometry and Amplex Red assays. Results: Acute stress increased AngII maximum contraction in Stressed Diabetic (SD)(E+)(Emax:0,88±0,05) or (E-)(Emax:1,38±0,06) when compared to Diabetic(E+)(Emax:0,70±0,04) and (E )(Emax:1,01±0,03). In the presence of PEG-Catalase Emax of SD(E+)(0,64±0,03), SD(E-)(1,21±0,05) and Diabetic(E+) (0,51±0,02) were reduced. Tiron also reduced Emax of SD(E+)(0,51±0,04), SD(E-)(1,17±0,05) and Diabetic(E+)(0,51±0,03). In presence of L-NNA it was observed reduced of  Emax  AngII Diabetic (E+) (0,69±0,04) and SD(E+)(0,68±0,03) which were accompanied with an increased protein expression of eNOSphospho-Ser1177 in the SD. The basal levels of O2- from Diabetic and SD rat carotid were higher when compared to the normoglycaemic group.3-Nitrotyrosine expression and H2O2 levels were increased in Diabetic carotid that were higher in the SD. VAS2870 reduced H2O2 levels from SD, without changing levels from control Diabetic. Conclusion: Our findings suggest that acute restraint stress exacerbates the contractile hyperreactivity to AngII in diabetic rat carotid by enhancing Nox4-driven generation of H2O2 and increased expression and activity of eNOS responsible for exacerbating the local peroxynitrite formation.

XV CONGRESSO BRASILEIRO DE ATEROSCLEROSE

18 e 19 de agosto de 2017

Realização

Departamento de Aterosclerose
SOLAT

Apoio

SBC

Secretaria Executiva

SD Eventos

Agência Web

Inteligência Web