Differential effects of jaundice and cirrhosis on β-adrenoceptor signaling in three rat models of cirrhotic cardiomyopathy
Section snippets
Chemical reagents and isotopes
cAMP protein binding assay kits were purchased from Amersham Canada Ltd. (Montreal, QC, Canada). Adenosine 5′-triphosphate (ATP), Guanosine 5′-triphosphate (GTP), (−)-isoproterenol (−)-bitartrate salt, sodium fluoride, aluminum chloride, and forskolin were purchased from Sigma Chemical Company (St. Louis, MO, USA). Other reagents were obtained either from Sigma or Fisher Scientific (Pittsburgh, PA, USA) and were the highest grade available.
Animal models
Male Sprague-Dawley rats (Bioscience Ltd, Calgary, AB
Histological and biochemical characteristics of the cirrhotic models
The liver architecture was severely deranged at 4 weeks after bile duct ligation surgery. Tremendous bile ductular proliferation was observed in portal areas. Fibrosis and hepatocyte necrosis were evident. Similar changes were observed in rats 10 days after undergoing choledochojejunostomy. In addition, after choledochojejunostomy, the liver and spleen weights were similar to the BDL rats, although the degree of ascites was decreased. Also, hepatocyte necrosis was less severe in the
Discussion
Over the past decade, we and others have been investigating the pathogenesis of cirrhotic cardiomyopathy 14., 16., 19., 20., 21. using the chronic bile duct-ligated rat, a model notable for deep jaundice. Because jaundice per se can induce blunted cardiac function 22., 23., this approach has been subject to the criticism that any observed changes could be due to the jaundice rather than cirrhosis. Accordingly, we felt that clarification of the roles and possible interaction between jaundice and
Acknowledgements
This study was funded by operating research grants from the Medical Research Council of Canada. Dr Ma was supported by a Canadian Liver Foundation Fellowship award and Dr Lee by an Alberta Heritage Foundation for Medical Research Scholarship award.
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