title: Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.
  
  
  METHODS
  Concentration-response curves for AngII were obtained in endothelium-intact or endothelium-denuded carotid rings, in the absence or presence of SC-560 (COX-1 inhibitor), SC-236 (COX-2 inhibitor), wortmannin (PI3K-Akt inhibitor), ML171 (NOX-1 inhibitor), VAS2870 (NOX-4 inhibitor), tiron (O2- scavenger) or PEG-catalase (H2O2scavenger). 6-ketoPGF1α, TXB2, O2- or H2O2levels and superoxide dismutase and catalase activity or expression were also measured in rat carotid.
  
  
  RESULTS
  Stress increased AngII potency in rat carotid. Muscular COX-1 or COX-2-derived metabolites negatively modulated AngII-induced contraction in control rat carotid. Endothelial COX-1 or COX-2-derived metabolites positively modulated AngII-induced contraction in stressed rat carotid. PI3K-Akt, NOX-1, NOX-4, O2- and H2O2positively modulated AngII-induced contraction in stressed rat carotid. Stress increased 6-ketoPGF1αor H2O2generation and reduced catalase activity in rat carotid. Protein expression of COX-1, NOX-4 or p-Akt was increased in stressed rat carotid.
  
  
  CONCLUSIONS
  Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI2and H2O2and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.
authors: Departament of Pharmacology, School of Medicine from Ribeirão Preto, Ribeirão Preto, SP, Brazil.|Laboratory of Vascular Injury, School of Pharmaceutical Sciences from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Hariane
authors: H
authors: Côco
authors: Laboratory of Vascular Injury, School of Pharmaceutical Sciences from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Larissa
authors: L
authors: Pernomian
authors: Departament of Pharmacology, School of Medicine from Ribeirão Preto, Ribeirão Preto, SP, Brazil.|Laboratory of Vascular Injury, School of Pharmaceutical Sciences from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Priscila C
authors: PC
authors: Pereira
authors: Laboratory of Vascular Injury, School of Pharmaceutical Sciences from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Mayara S
authors: MS
authors: Gomes
authors: Departament of Pharmacology, School of Medicine from Ribeirão Preto, Ribeirão Preto, SP, Brazil.|Laboratory of Pharmacology, School of Nursing from Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors: Katia C
authors: KC
authors: Marchi
authors: Departament of Pharmacology, School of Medicine from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Alexandre H
authors: AH
authors: Lopes
authors: Departament of Pharmacology, School of Medicine from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Thiago M
authors: TM
authors: Cunha
authors: Laboratory of Pharmacology, School of Nursing from Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.
authors: Carlos R
authors: CR
authors: Tirapelli
authors: Laboratory of Vascular Injury, School of Pharmaceutical Sciences from Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors: Ana M
authors: AM
authors: de Oliveira
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D004730:Endothelium, Vascular / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D010069:Oxadiazoles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D014661:Vasoconstriction
chemical_list: C547311:4-(3-acetyl-5-(pyridine-3-yl)-2,3-dihydro-1,3,4-oxadiazole-2-yl)phenyl acetate; D016861:Cyclooxygenase Inhibitors; D010069:Oxadiazoles; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D015121:6-Ketoprostaglandin F1 alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003345:Corticosterone
keywords: Akt; angiotensin II; chronic restraint stress; hydrogen peroxide; prostacyclin