Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension
Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension
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DOI：
10.1097/01.hjh.0000166844.42227.5c
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发表时间：
2005-05-01
影响因子：
4.9
通讯作者：
Oriowo, MA
中科院分区：
文献类型：
--
作者：
Adeagbo, ASO;Zhang, XD;Oriowo, MA
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(ill) 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 degrees C) and bubbled with a 5%CO2/95%O-2 gas mixture. Aortic sensitivities (pD(2) values) to norepinephrine and serum isoprostanes (8-isoprostaglandin F-2 alpha, 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 pD(2) 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. (c) 2005 Lippincott Williams & Wilkins.
