{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:46:20Z","timestamp":1792676780484,"version":"4.5.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6666,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The pathogenesis of cirrhotic cardiomyopathy remains unclear. Because ventricular contractility is dependent on the interplay of stimulatory \u03b2-adrenergic and inhibitory muscarinic receptors, we aimed to examine a possible role of muscarinic M2 receptor overactivity in a rat model of cirrhotic cardiomyopathy. Cirrhosis was induced by bile duct ligation (BDL), while controls underwent sham operations. Contractile responses to the muscarinic agonist carbachol were measured <jats:italic toggle=\"yes\">in situ<\/jats:italic> in the autonomic-denervated pithed rat and <jats:italic toggle=\"yes\">in vitro<\/jats:italic> in isolated ventricular papillary muscles. Ventricular sarcolemmal plasma membranes were isolated by sucrose density gradients, and muscarinic receptor characteristics were studied using 1-[<jats:italic toggle=\"yes\">N<\/jats:italic>-methyl-<jats:sup>3<\/jats:sup>H]scopolamine (NMS). Membrane adenylyl cyclase activity was tested by a protein binding assay. Maximum first time derivative of peak ventricular systolic pressure (+dP\/dt) for sham-operated and cirrhotic rats at baseline was 3,599 \u00b1 296 versus 1,226 \u00b1 63 mm Hg\/sec (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .01). Maximum first time derivative of ventricular diastolic relaxation (-dP\/dt) for sham and cirrhotic rats at basal levels was -3,040 \u00b1 235 versus -864 \u00b1 59 (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .01). The +dP\/dt<jats:sub>max<\/jats:sub>, and -dP\/dt<jats:sub>max<\/jats:sub> responses to carbachol were blunted in the cirrhotic rats. The cirrhotic papillary muscles showed significantly less inhibition to incremental doses of carbachol than control rat muscles. Likewise, isoproterenol-stimulated membrane adenylyl cyclase activity was significantly less inhibited by carbachol doses in the cirrhotic rats. Membrane M2 receptor density and binding affinity in cirrhotic rat hearts were similar to controls. We conclude that muscarinic responsiveness was blunted in cirrhotic hearts, but this was not caused by receptor down-regulation, suggesting changes in postreceptor factors. These changes in muscarinic function are likely compensatory, and M2 receptor overactivity is not involved in the genesis of cirrhotic cardiomyopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510250610","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:06:43Z","timestamp":1090969603000},"page":"1361-1365","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":60,"title":["Cardiac muscarinic receptor function in rats with cirrhotic cardiomyopathy"],"prefix":"10.1097","volume":"25","author":[{"given":"D N","family":"Jaue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S S","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510250610","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199706000-00011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T15:21:26Z","timestamp":1738941686000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199706000-00011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1997]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510250610","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1997,6]]}}}