{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:52:33Z","timestamp":1791053553586,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2799,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Endotoxin\u2010induced vascular hyporeactivity to phenylephrine (PE) is well described in rodent aorta, but has not been investigated in smaller vessels <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Segments of rat superior mesenteric artery were incubated in culture medium with or without foetal bovine serum (10%) for 6, 20 or 46\u2003h in the presence or absence of bacterial lipopolysaccharide (LPS; 1\u2003\u2013\u2003100\u2003\u03bcg\u2003ml<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Contractions to PE were measured with or without nitric oxide synthase (NOS) inhibitors: <jats:sc>L<\/jats:sc>\u2010NAME (300\u2003\u03bc<jats:sc>M<\/jats:sc>), aminoguanidine (AMG; 400\u2003\u03bc<jats:sc>M<\/jats:sc>) 1400W (10\u2003\u03bc<jats:sc>M<\/jats:sc>) and GW273629 (10\u2003\u03bc<jats:sc>M<\/jats:sc>); the guanylyl cyclase inhibitor, ODQ (3\u2003\u03bc<jats:sc>M<\/jats:sc>); the COX\u20102 inhibitor, NS\u2010398 (10\u2003\u03bc<jats:sc>M<\/jats:sc>). Contractile responses to the thromboxane A<jats:sub>2<\/jats:sub> mimetic, U46619 were also assessed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the presence of serum, LPS induced hyporeactivity at all time points. In its absence, hyporeactivity only occurred at 6 and 20\u2003h.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:sc>L<\/jats:sc>\u2010NAME and AMG fully reversed hyporeactivity at 6\u2003h, whereas they were only partially effective at 20\u2003h and not at all at 46\u2003h. In contrast partial reversal of peak contraction was observed with 1400W (62% at 46\u2003h), GW273629 (57% at 46\u2003h) and ODQ (75% at 46\u2003h). COX\u20102 inhibition produced no reversal.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In contrast to PE, contractions to U46619 were substantially less affected by LPS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We describe a well\u2010characterized reproducible model of LPS\u2010induced hyporeactivity, which is largely mediated by the NO\u2010cyclic GMP\u2010dependent pathway. Importantly, long\u2010term (2\u2010day) production of NO <jats:italic>via<\/jats:italic> iNOS is demonstrated. Moreover, conventional doses of <jats:sc>L<\/jats:sc>\u2010NAME and AMG became increasingly ineffective over time. Thus, the choice of inhibitor merits careful consideration in long\u2010term models.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>133<\/jats:bold>, 351\u2013360; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704079\">10.1038\/sj.bjp.0704079<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704079","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:27:50Z","timestamp":1106947670000},"page":"351-360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Temporal variation in endotoxin\u2010induced vascular hyporeactivity in a rat mesenteric artery organ culture model"],"prefix":"10.1111","volume":"133","author":[{"given":"A J","family":"O'Brien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Sibbald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L H","family":"Clapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702590"},{"key":"e_1_2_7_3_1","first-page":"3049","article-title":"Endotoxin\u2010mediated endothelial cell injury and activation: role of soluble CD14","volume":"60","author":"ARDITI M.","year":"1993","journal-title":"Infect. 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