{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:32:32Z","timestamp":1791207152863,"version":"4.1.0"},"reference-count":35,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,2,1]]},"abstract":"<jats:p>We have demonstrated recently [Callera, Touyz, Teixeira, Muscara, Carvalho, Fortes, Schiffrin and Tostes (2003) Hypertension 42, 811\u2013817] that increased vascular oxidative stress in DOCA (deoxycorticosterone acetate)-salt rats is associated with activation of the ET (endothelin) system via ETA receptors. The exact source of ET-1-mediated oxidative stress remains unclear. The aim of the present study was to investigate whether ET-1 increases generation of ROS (reactive oxygen species) in DOCA-salt hypertension through NADPH-oxidase-dependent mechanisms. Xanthine oxidase, eNOS (endothelial nitric oxide synthase) and COX-2 (cyclo-oxygenase-2) were also examined as potential ET-1 sources of ROS as well as mitochondrial respiration. DOCA-salt and control UniNX (uninephrectomized) rats were treated with the ETA antagonist BMS182874 (40\u00a0mg\u00b7day\u22121\u00b7kg\u22121 of body weight) or vehicle. Plasma TBARS (thiobarbituric acid-reacting substances) were increased in DOCA-salt compared with UniNX rats. Activity of NADPH and xanthine oxidases in aorta, mesenteric arteries and heart was increased in DOCA-salt rats. BMS182874 decreased plasma TBARS levels without influencing NADPH and xanthine oxidase activities in DOCA-salt rats. Increased p22phox protein expression and increased p47phox membrane translocation in arteries from DOCA-salt by rats were not affected by BMS182874 treatment. Increased eNOS and COX-2 expression, also observed in aortas from DOCA-salt rats, was unaltered by BMS182874. Increased mitochondrial generation of ROS in DOCA-salt rats was normalized by BMS182874. ETA antagonism also increased the expression of mitochondrial MnSOD (manganese superoxide dismutase) in DOCA-salt rats. In conclusion, activation of NADPH oxidase does not seem to be the major source of oxidative stress induced by ET-1\/ETA in DOCA-salt hypertension, which also appears to be independent of increased activation of xanthine oxidase or eNOS\/COX-2 overexpression. Mitochondria may play a role in ET-1-driven oxidative stress, as evidenced by increased mitochondrial-derived ROS in this model of hypertension.<\/jats:p>","DOI":"10.1042\/cs20050307","type":"journal-article","created":{"date-parts":[[2006,1,26]],"date-time":"2006-01-26T12:09:54Z","timestamp":1138277394000},"page":"243-253","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms"],"prefix":"10.1042","volume":"110","author":[{"given":"Glaucia\u00a0E.","family":"Callera","sequence":"first","affiliation":[{"name":"Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita\u00a0C.","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Yogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto\u00a0C.\u00a0I.","family":"Montezano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhian\u00a0M.","family":"Touyz","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2006,1,17]]},"reference":[{"key":"2021120120461431800_B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1586\/14779072.1.1.91","article-title":"Reactive oxygen species in vascular biology: role in arterial hypertension","volume":"1","author":"Touyz","year":"2003","journal-title":"Expert. 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