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A new strategy to ameliorate endotoxemic hypotension by inducing endothelium\u2010dependent constriction of large arteries was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Endotoxemia in rats was induced by injection of LPS (10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v.). Haemodynamics were measured <jats:italic>in vivo<\/jats:italic>, reactivity of isolated mesenteric arteries by myography and expression of proteins and enzyme activities by immunohistochemistry, biochemistry and molecular biology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key ResultS<\/jats:title><jats:p>Six hours after LPS, the hypotension was promptly reversed following injection (i.v. or i.p.) of oroxylin\u2010A (OroA) . In isolated LPS\u2010treated but not normal mesenteric arteries, OroA (1\u201310\u00a0\u03bcM) induced endothelium\u2010dependent, sustained constriction, blocked by endothelin\u20101 (ET\u20101) receptor antagonists. OroA further enhanced LPS\u2010induced expression of endothelin\u2010converting enzyme, ET\u20101 mRNA and proteins and ET\u20101 release, OroA also enhanced phosphorylation of Rho\u2010associated protein kinase (ROCK) and reversed LPS\u2010induced suppression of RhoA activities in smooth muscle of arteries with endothelium. Activated\u2010 phosphorylation of smooth muscle ROCK was blocked by ET\u20101\u2010receptor antagonists and ROCK inhibitors. Moreover, OroA post\u2010treatment suppressed, via inhibiting NF\u2010\u03baB activation, inducible NOS expression and circulating NO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Reversal of endotoxemic hypotensive by OroA was due to release of endothelial ET\u20101, upregulated by LPS, from mesenteric arteries, inducing prompt and sustained vasoconstriction via activation of vascular smooth muscle RhoA \/ ROCK\u2010pathway. In late endotoxemia, OroA\u2010induced vasoconstriction was partly due to decreased circulating NO. Activation of endothelium\u2010dependent constriction in large resistance arteries and suppression of systemic inflammation offer new strategies for acute management of endotoxemic hypotensive shock.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13415","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T02:19:10Z","timestamp":1450837150000},"page":"1179-1195","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Induction of endothelium\u2010dependent constriction of mesenteric arteries in endotoxemic hypotensive shock"],"prefix":"10.1111","volume":"173","author":[{"given":"Tzu\u2010Ling","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Medical Research Buddhist Tzu Chi General Hospital  Hualien Taiwan"},{"name":"Institutes of Medical Sciences and Pharmacology &amp; Toxicology  Hualien Taiwan"},{"name":"Department of Life Sciences Tzu Chi Center of Vascular Medicine, College of Life Sciences  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research Buddhist Tzu Chi General Hospital  Hualien Taiwan"},{"name":"Department of Life Sciences Tzu Chi Center of Vascular Medicine, College of Life Sciences  Hualien Taiwan"},{"name":"Tzu Chi College of Technology  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin\u2010Hung","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Research Buddhist Tzu Chi General Hospital  Hualien Taiwan"},{"name":"Institutes of Medical Sciences and Pharmacology &amp; Toxicology  Hualien Taiwan"},{"name":"Department of Life Sciences Tzu Chi Center of Vascular Medicine, College of Life Sciences  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Yoong","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Buddhist Tzu Chi General Hospital  Hualien Taiwan"},{"name":"Institutes of Medical Sciences and Pharmacology &amp; Toxicology  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung\u2010Hsiang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institutes of Medical Sciences and Pharmacology &amp; Toxicology  Hualien Taiwan"},{"name":"Department of Pathology, College of Medicine Tzu Chi University  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony J F","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Research Buddhist Tzu Chi General Hospital  Hualien Taiwan"},{"name":"Institutes of Medical Sciences and Pharmacology &amp; Toxicology  Hualien Taiwan"},{"name":"Department of Life Sciences Tzu Chi Center of Vascular Medicine, College of Life Sciences  Hualien Taiwan"},{"name":"Department of Pharmacology Southern Illinois University School of Medicine  Springfield IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1887"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","unstructured":"Arqu\u00e9sO ChicoteI TenbaumS PuigI PalmerGH(2012).Standardized Relative Quantification of Immunofluorescence Tissue Staining. 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