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This study assessed the role of NO in the vasoconstrictor hyporeactivity of portal vein\u2010ligated (PVL) rats in isolated and <jats:italic>in situ<\/jats:italic> perfused mesenteric arterial beds.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Isolated perfused mesenteric arteries of PVL rats were significantly less reactive to noradrenaline (NA), methoxamine (METH), arginine vasopressin (AVP) and endothelin\u20101 (ET\u20101) than those from sham\u2010operated (Sham) rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Blockade of NO synthesis with N<jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine methyl ester (<jats:sc>L<\/jats:sc>\u2010NAME, 100\u2003\u03bc<jats:sc>M<\/jats:sc>) in isolated perfused mesenteric arteries from PVL rats restored the reactivity to bolus injections of AVP and ET\u20101, but had little effect on the hyporeactivity to NA or METH. Cyclo\u2010oxygenase inhibition with indomethacin (5\u2003\u03bc<jats:sc>M<\/jats:sc>) likewise did not restore reactivity to METH of isolated perfused mesenteric arteries of PVL rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The hyporeactivity to METH seen in isolated perfused mesenteric arteries from PVL rats was reduced by low concentrations of AVP (20\u2003n<jats:sc>M<\/jats:sc>) or ET\u20101 (1\u2003n<jats:sc>M<\/jats:sc>) which <jats:italic>per se<\/jats:italic> caused only a slight increase in perfusion pressure. When <jats:sc>L<\/jats:sc>\u2010NAME (100\u2003\u03bc<jats:sc>M<\/jats:sc>) was combined with AVP (20\u2003n<jats:sc>M<\/jats:sc>) or ET\u20101 (1\u2003n<jats:sc>M<\/jats:sc>), respectively, reactivity to METH of isolated perfused mesenteric arteries of PVL rats was restored to the level seen in Sham rats. These effects of AVP and ET\u20101 were not mimicked by precontracting the vessels with 5\u2010hydroxytryptamine (5\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The differential effects of <jats:sc>L<\/jats:sc>\u2010NAME and AVP on the hyporesponsiveness to methoxamine and AVP were corroborated by experiments performed with the <jats:italic>in situ<\/jats:italic> perfused mesenteric vascular bed preparation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data indicate that both NO\u2010dependent and NO\u2010independent mechanisms are involved in the vasoconstrictor hyporesponsiveness of mesenteric arteries from portal hypertensive rats. The hyporeactivity to AVP and ET\u20101 is mediated by NO whereas the reduced responsiveness to adrenoceptor agonists appears to be predominantly NO\u2010independent. AVP and ET\u20101, in addition, seem to inhibit the NO\u2010independent mechanism of vascular hyporeactivity, since the hyporesponsiveness to METH was reduced in the presence of AVP or ET\u20101 and abolished by the combination of these peptides with <jats:sc>L<\/jats:sc>\u2010NAME.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701220","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:11:32Z","timestamp":1156525892000},"page":"1031-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nitric oxide\u2010dependent and \u2010independent vascular hyporeactivity in mesenteric arteries of portal hypertensive rats"],"prefix":"10.1111","volume":"121","author":[{"given":"Akos","family":"Heinemann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof H","family":"Wachter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Holzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fickert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf E","family":"Stauber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199303000-00011"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90920-7"},{"key":"e_1_2_5_4_1","first-page":"G486","article-title":"Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension","volume":"247","author":"Benoit J.N.","year":"1984","journal-title":"Am. 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