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Am J Physiol Gastrointest Liver Physiol (August 14, 2008). doi:10.1152/ajpgi.90352.2008
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Submitted on May 23, 2008
Revised on July 5, 2008
Accepted on August 6, 2008

Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Leila Moezi1, Seyed Ali Gaskari2, and Samuel S. Lee2*

1 University of Shiraz Faculty of Pharmacy and Pharmacology
2 University of Calgary

* To whom correspondence should be addressed. E-mail: samlee{at}ucalgary.ca.

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.




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
X. Sun, A. Cardenas, Y. Wu, K. Enjyoji, and S. C. Robson
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Am J Physiol Gastrointest Liver Physiol, August 1, 2009; 297(2): G306 - G311.
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