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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/G649    most recent ajpgi.90352.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Moezi, L. Articles by Lee, S. S. Search for Related Content PubMed PubMed Citation Articles by Moezi, L. Articles by Lee, S. S.

THEMES

Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

¹Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; ²Liver Unit, Faculty of Medicine, University of Calgary, Calgary, Canada

Submitted 23 May 2008 ; accepted in final form 6 August 2008

Cirrhosis is associated with marked cardiovascular disturbances. These include hyperdynamic circulation characterized by reduced peripheral vascular resistance and mean arterial pressure and increased cardiac output. Despite the baseline increase in cardiac output, ventricular responsiveness to stimuli is blunted. A number of cellular signaling pathways have been shown to contribute to these abnormalities, including central nervous system cardiovascular dysregulation and humoral factors such as nitric oxide. Endogenous and exogenous cannabinoids have significant cardiovascular effects. Recent evidence suggests that increased activity of the endocannabinoid system at multiple levels contributes to development of both cardiac and vascular changes in cirrhosis. This brief review surveys recent in vivo and in vitro findings in an attempt to highlight the areas of agreement and areas of controversy in the field. The endocannabinoid system affects key cardiovascular regulators, including the autonomic nervous system, cardiac muscle, and vascular smooth muscle. The interplay among these modes of action further complicates interpretation of the in vivo findings. The broad range of cardiovascular actions of endocannabinoids provides ample opportunities for pharmacological manipulation. At the same time, it increases the possibility of undesirable side effects, which need to be carefully evaluated in long-term studies.

portal hypertension; vanilloid; anandamide; cirrhotic cardiomyopathy

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