The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

Autor(es)

Pernomian, Larissa ^{[1, 2]} ; Gomes, Mayara Santos ^[1] ; Araujo Restini, Carolina Baraldi ^[3] ; Zambelli Ramalho, Leandra Naira ^[4] ; Tirapelli, Carlos Renato ^[5] ; de Oliveira, Ana Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Pharmacol Lab, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Pharmacol Lab, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Ribeirao Preto, Dept Med, BR-14096900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Lab Cellular & Mol Pathol, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, Pharmacol Lab, BR-14040902 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 678, n. 1-3, p. 15-25, MAR 5 2012.
• Citações Web of Science: 24

Resumo

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin {[}NAD(P) H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells. Cyclooxygenase and AT1-receptor expression was assessed by immunohistochemistry. Diabetes increased the angiotensin II-induced contraction but reduced the agonist potency in rat carotid. Endothelium removal, tiron or apocynin restored the angiotensin II-induced contraction in diabetic rat carotid to control levels. PEG-catalase, DMTU or SC560 reduced the angiotensin II-induced contraction in diabetic rat carotid at the same extent. SC236 restored the angiotensin II potency in diabetic rat carotid. Y-27632 reduced the angiotensin II-induced contraction in endothelium-intact or -denuded diabetic rat carotid. Diabetes increased the DHE-fluorescence of carotid endothelial cells. Apocynin reduced the DHE-fluorescence of endothelial cells from diabetic rat carotid to control levels. Diabetes increased the muscular cyclooxygenase-2 expression but reduced the muscular AT1-receptor expression in rat carotid. In summary, hydroxyl radical, hydrogen peroxide and superoxide anion-derived from endothelial NAD(P) H oxidase mediate the hyperreactivity to angiotensin II in type I-diabetic rat carotid, involving the participation of cyclooxygenase-1 and Rho-kinase. Moreover, increased muscular cyclooxygenase-2 expression in type I-diabetic rat carotid seems to be related to the local reduced AT1-receptor expression and the reduced angiotensin II potency. (C) 2011 Elsevier B. V. All rights reserved. (AU)

• Processo FAPESP: 09/01005-0 - Influência do estresse oxidativo sobre a resposta à angiotensina II em carótida contra-lateral à lesão por catéter-balão de rato diabético
• Beneficiário: Larissa Pernomian
• Modalidade de apoio: Bolsas no Brasil - Doutorado