{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:53:09Z","timestamp":1788472389879,"version":"build-2803163510"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>In cirrhosis, 11,12\u2010epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of <jats:italic toggle=\"yes\">in vivo<\/jats:italic> inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride\u2010induced cirrhosis were studied. Eight controls and eight rats with cirrhosis were treated with the specific epoxygenase inhibitor <jats:italic toggle=\"yes\">N<\/jats:italic>\u2010(methylsulfonyl)\u20102\u2010(2\u2010propynyloxy)\u2010benzenehexanamide (MS\u2010PPOH; 20 mg\/kg\/day) for 3 consecutive days. Portal blood flow and renal and splenic resistive indexes were calculated through echographic measurements, while portal and systemic pressures were measured through polyethylene\u221250 catheters. Small resistance mesenteric arteries were connected to a pressure servo controller in a video\u2010monitored perfusion system, and concentration\u2010response curves to phenylephrine and acetylcholine were evaluated. EET levels were measured in tissue homogenates of rat liver, kidney, and aorta, using an enzyme\u2010linked immunosorbent assay. Urinary Na<jats:sup>+<\/jats:sup> excretion function was also evaluated. In rats with cirrhosis, treatment with MS\u2010PPOH significantly reduced portal blood flow and portal pressure compared to vehicle (13.6 \u00b1 5.7 versus 25.3 \u00b1 7.1 mL\/min\/100 g body weight, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05; 9.6 \u00b1 1.1 versus 12.2 \u00b1 2.3 mm Hg, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05; respectively) without effects on systemic pressure. An increased response to acetylcholine of mesenteric arteries from rats with cirrhosis (50% effect concentration \u20107.083 \u00b1 0.197 versus \u20106.517 \u00b1 0.73 in control rats, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05) was reversed after inhibition of EET production (\u20106.388 \u00b1 0.263, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). In liver, kidney, and aorta from animals with cirrhosis, treatment with MS\u2010PPOH reversed the increase in EET levels. In both controls and rats with cirrhosis, MS\u2010PPOH increased urinary Na<jats:sup>+<\/jats:sup> excretion. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: In rats with cirrhosis, <jats:italic toggle=\"yes\">in vivo<\/jats:italic> inhibition of EET production normalizes the response of mesenteric arteries to vasodilators, with beneficial effects on portal hypertension. (H<jats:sc>epatology<\/jats:sc> 2016;64:923\u2010930)<\/jats:p>","DOI":"10.1002\/hep.28686","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T01:23:35Z","timestamp":1466126615000},"page":"923-930","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation"],"prefix":"10.1097","volume":"64","author":[{"given":"Marco","family":"Di Pascoli","sequence":"first","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Verardo","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Turato","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Angeli","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacerdoti","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Bolognesi","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,7,22]]},"reference":[{"key":"hep28686-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0168-8278(85)80770-4","article-title":"Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators","volume":"1","year":"1985","journal-title":"J Hepatol"},{"key":"hep28686-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/0016-5085(94)90251-8","article-title":"Impaired responsiveness to endogenous vasoconstrictors and endothelium\u2010derived vasoactive factors in 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