title: Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.
abstract: We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.
authors.affiliation: Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP) , Ribeirão Preto, São Paulo , Brazil .
authors.forename: Ana P P
authors.initials: AP
authors.lastname: Carda
authors.forename: Katia C
authors.initials: KC
authors.lastname: Marchi
authors.forename: Elen
authors.initials: E
authors.lastname: Rizzi
authors.forename: André S
authors.initials: AS
authors.lastname: Mecawi
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Padovan
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D005978:Glutathione / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012701:Serotonin / Q000494:pharmacology; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008565:Membrane Proteins; D011453:Prostaglandins; D017392:Thiobarbituric Acid Reactive Substances; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012701:Serotonin; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D013929:Thromboxane B2; C045749:SQ 29548; D015237:Dinoprost; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: Cyclooxygenase; hypertension; nitric oxide; reactive oxygen species; superoxide anion; vascular reactivity