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• W2093157068 abstract "Objective To test the hypothesis that the enhanced vascular responsiveness to norepinephrine that occurs during deoxycorticosterone acetate (DOCA)-salt induced hypertension is causally related to increased expression of cyclo-oxygenase (COX)-2 and oxidative stress, which diminishes the vasomodulatory influence of endothelium-derived nitric oxide. Methods Four groups of age-matched, male Sprague–Dawley rats were studied: Sham (normotensive); DOCA-salt (hypertensive); DOCA-salt treated with manganese(III) tetra(4-benzoic acid) porphyrin chloride [MnTBAP, an antioxidant; 15 mg/kg intraperitoneally (i.p.) for 21 days]; DOCA-salt treated with {N-[2-(cyclohexyloxy)-4-nitrophenyl]-methane sulfonamide} (NS-398, a COX-2 selective blocker; 5 mg/kg i.p. for 7 days). Contraction and relaxation were measured with FT03 force transducers coupled to a Grass polygraph in aortic rings bathed with physiologic salt solution (37°C) and bubbled with a 5%CO2/95%O2 gas mixture. Aortic sensitivities (pD2 values) to norepinephrine and serum isoprostanes (8-iso-prostaglandin F2α, a marker of oxidative stress) were measured for each experimental paradigm. Results NS-398 significantly reduced maximal contractions in response to norepinephrine in aortic rings from Sham (44 ± 3%) and DOCA-salt (96 ± 2%) group rats. Expression of COX-2 protein increased significantly in vessels from DOCA-salt rats compared with those from Sham group rats. Treatment of DOCA-salt rats with either MnTBAP or NS-398 alleviated hypertension, normalized aortic pD2 values for norepinephrine and restored serum 8-isoprostane concentrations towards those observed in Sham group rats. Conclusions COX-2 expression increases during DOCA-salt hypertension, and mediates production of factors that enhance rat aortic contractility in response to norepinephrine. Our data also suggest a role for increased oxidative stress, which is at least in part dependent on enhanced COX-2 expression, in the mechanism(s) of enhanced aortic contractility in response to norepinephrine during DOCA-salt hypertension." @default.
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• W2093157068 date "2005-05-01" @default.
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• W2093157068 title "Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension" @default.
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• W2093157068 doi "https://doi.org/10.1097/01.hjh.0000166844.42227.5c" @default.
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