{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T18:38:56Z","timestamp":1761935936411,"version":"build-2065373602"},"reference-count":36,"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":3408,"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":[[1999,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Tumour necrosis factor (TNF\u2010\u03b1) is involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. On the other hand, inhibition of TNF\u2010\u03b1 is an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock. We therefore investigated the effects of the melanocortin peptide ACTH\u2010(1\u201324) (adrenocorticotropin fragment 1\u201324) on the vascular failure induced by SAO shock.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SAO\u2010shocked rats had a decreased survival rate (0% at 4\u2003h of reperfusion, while sham\u2010shocked rats survived for more than 4\u2003h), enhanced serum TNF\u2010\u03b1 concentrations (755\u00b181\u2003U\u2003ml<jats:sup>\u22121<\/jats:sup>), decreased mean arterial blood pressure, leukopenia, and increased ileal leukocyte accumulation, as revealed by means of myeloperoxidase activity (MPO=9.4\u00b11\u2003U\u2003g<jats:sup>\u22121<\/jats:sup> tissue). Moreover, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1\u2003n<jats:sc>M<\/jats:sc>\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>) (E<jats:sub>max<\/jats:sub> and ED<jats:sub>50<\/jats:sub> in shocked rats=7.16\u2003mN\u2003mg<jats:sup>\u22121<\/jats:sup> tissue and 120\u2003n<jats:sc>M<\/jats:sc>, respectively; E<jats:sub>max<\/jats:sub> and ED<jats:sub>50<\/jats:sub> in sham\u2010shocked rats=16.31\u2003mN\u2003mg<jats:sup>\u22121<\/jats:sup> tissue and 100\u2003n<jats:sc>M<\/jats:sc>, respectively), reduced responsiveness to acetylcholine (ACh, 10\u2003n<jats:sc>M<\/jats:sc>\u201010\u2003\u03bc<jats:sc>M<\/jats:sc>) (E<jats:sub>max<\/jats:sub> and ED<jats:sub>50<\/jats:sub> in shocked rats=30% relaxation and 520\u2003n<jats:sc>M<\/jats:sc>, respectively; E<jats:sub>max<\/jats:sub> and ED<jats:sub>50<\/jats:sub> in sham\u2010shocked rats=82% relaxation and 510\u2003n<jats:sc>M<\/jats:sc>, respectively) and increased staining for intercellular adhesion molecule\u20101 (ICAM\u20101).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ACTH\u2010(1\u201324) [160\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup> intravenously (i.v.), 5\u2003min after SAO] increased survival rate [SAO+ACTH\u2010(1\u201324)=80% at 4\u2003h of reperfusion], reversed hypotension, reduced serum TNF\u2010\u03b1 (55\u00b113\u2003U\u2003ml<jats:sup>\u22121<\/jats:sup>), ameliorated leukopenia, reduced ileal MPO (1.2\u00b10.2\u2003U\u2003g<jats:sup>\u22121<\/jats:sup> tissue), restored the reactivity to PE, improved the responsiveness to ACh and blunted the enhanced immunostaining for ICAM\u20101 in the aorta.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Adrenalectomy only in part\u2013but not significantly\u2013reduced the ACTH\u2010induced shock reversal, the survival rate of SAO+ACTH\u2010(1\u201324) adrenalectomized rats being 60% at 4\u2003h of reperfusion; and methylprednisolone (80\u2003mg<jats:sup>\u22121<\/jats:sup> i.v., 5\u2003min after SAO) had a non\u2010significant effect (10% survival) at 4\u2003h of reperfusion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present data show that melanocortins are effective also in SAO shock, their effect being, at least in part, mediated by reduced production of TNF\u2010\u03b1. Furthermore, they demonstrate, for the first time, that this inhibition is responsible for the adrenocorticotropin\u2010induced reversal of vascular failure and leukocyte accumulation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 816\u2013822; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702848\">10.1038\/sj.bjp.0702848<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702848","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:12:18Z","timestamp":1106943138000},"page":"816-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Adrenocorticotropin reverses vascular dysfunction and protects against splanchnic artery occlusion shock"],"prefix":"10.1111","volume":"128","author":[{"given":"Francesco","family":"Squadrito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Guarini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenica","family":"Altavilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Squadrito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe M","family":"Campo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarita","family":"Arlotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Quartarone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonino","family":"Saitta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Cucinotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Bazzani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria M","family":"Cainazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Mioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfio","family":"Bertolini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille P","family":"Caputi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"584","article-title":"HP\u2010228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro","volume":"275","author":"ABOU\u2010MOHAMED G.","year":"1995","journal-title":"J. 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