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Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on <jats:italic>\u03b2<\/jats:italic>\u2010adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10<jats:sup>\u22126<\/jats:sup>\u2003<jats:sc>m<\/jats:sc>), <jats:italic>N<\/jats:italic>(<jats:italic>\u03c9<\/jats:italic>)\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME, 10<jats:sup>\u22124<\/jats:sup>\u2003<jats:sc>m<\/jats:sc>), and naltrexone plus <jats:sc>l<\/jats:sc>\u2010NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3\u2003\u00d7\u200310<jats:sup>\u22124<\/jats:sup>\u2003<jats:sc>m<\/jats:sc>). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham\u2010operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half\u2010maximal effective concentrations of isoproterenol in these concentration\u2013response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, <jats:sc>l<\/jats:sc>\u2010NAME and aminoguanidine. Concurrent administration of naltrexone and <jats:sc>l<\/jats:sc>\u2010NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to <jats:italic>\u03b2<\/jats:italic>\u2010adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO\u2010induced hyporesponsiveness to <jats:italic>\u03b2<\/jats:italic>\u2010adrenergic stimulation in cirrhosis.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2006.00431.x","type":"journal-article","created":{"date-parts":[[2006,7,24]],"date-time":"2006-07-24T09:03:59Z","timestamp":1153731839000},"page":"461-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to <i>\u03b2<\/i>\u2010adrenergic stimulation in cirrhotic rats"],"prefix":"10.1111","volume":"20","author":[{"given":"Farzad","family":"Ebrahimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Tavakoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Reza","family":"Hajrasouliha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Sadeghipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Dehghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Hossein","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Reza","family":"Dehpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91384-7"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260507"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0970259"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.2.268"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90940-D"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(95)80286-X"},{"key":"e_1_2_6_8_2","first-page":"435","article-title":"Cause of death after liver transplantation: an analysis of 41 cases in 382 patients","volume":"120","author":"Rayes N.","year":"1995","journal-title":"Zentralbl. 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