HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1689    most recent 00538.2007v1 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 ISI 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 ISI Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Bátkai, S. Articles by Kunos, G. Search for Related Content PubMed PubMed Citation Articles by Bátkai, S. Articles by Kunos, G.

Endocannabinoids acting at CB₁ receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats

Sections on ¹Neuroendocrinology and ²Oxidative Stress and Tissue Injury, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland

Submitted 7 May 2007 ; accepted in final form 3 June 2007

Advanced liver cirrhosis is associated with hyperdynamic circulation consisting of systemic hypotension, decreased peripheral resistance, and cardiac dysfunction, termed cirrhotic cardiomyopathy. Previous studies have revealed the role of endocannabinoids and vascular CB₁ receptors in the development of generalized hypotension and mesenteric vasodilation in animal models of liver cirrhosis, and CB₁ receptors have also been implicated in the decreased -adrenergic responsiveness of isolated heart tissue from cirrhotic rats. Here we document the cardiac contractile dysfunction in vivo in liver cirrhosis and explore the role of the endocannabinoid system in its development. Rats with CCl₄-induced cirrhosis developed decreased cardiac contractility, as documented through the use of the Millar pressure-volume microcatheter system, low blood pressure, and tachycardia. Bolus intravenous injection of the CB₁ antagonist AM251 (3 mg/kg) acutely increased mean blood pressure, as well as both load-dependent and -independent indexes of systolic function, whereas no such changes were elicited by AM251 in control rats. Furthermore, tissue levels of the endocannabinoid anandamide increased 2.7-fold in the heart of cirrhotic compared with control rats, without any change in 2-arachidonoylglycerol levels, whereas, in the cirrhotic liver, both 2-arachidonoylglycerol (6-fold) and anandamide (3.5-fold) were markedly increased. CB₁-receptor expression in the heart was unaffected by cirrhosis, as verified by Western blotting. Activation of cardiac CB₁ receptors by endogenous anandamide contributes to the reduced cardiac contractility in liver cirrhosis, and CB₁-receptor antagonists may be used to improve contractile function in cirrhotic cardiomyopathy and, possibly, in other forms of heart failure.

cirrhosis; cannabinoid CB₁ receptors; endocannabinoids; cardiac contractility; pressure-volume loops

This article has been cited by other articles:

				N. Defer, J. Wan, R. Souktani, B. Escoubet, M. Perier, P. Caramelle, S. Manin, V. Deveaux, M.-C. Bourin, A. Zimmer, et al. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy FASEB J, July 1, 2009; 23(7): 2120 - 2130. [Abstract] [Full Text] [PDF]

				D. S. Hydock, C.-Y. Lien, and R. Hayward Anandamide Preserves Cardiac Function and Geometry in an Acute Doxorubicin Cardiotoxicity Rat Model Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2009; 14(1): 59 - 67. [Abstract] [PDF]

				F. Dol-Gleizes, R. Paumelle, V. Visentin, A.-M. Mares, P. Desitter, N. Hennuyer, A. Gilde, B. Staels, P. Schaeffer, and F. Bono Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, Inhibits Atherosclerosis in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2009; 29(1): 12 - 18. [Abstract] [Full Text] [PDF]

				S Moller and J H Henriksen Cardiovascular complications of cirrhosis Postgrad. Med. J., January 1, 2009; 85(999): 44 - 54. [Abstract] [Full Text] [PDF]

				L. Moezi, S. A. Gaskari, and S. S. Lee Endocannabinoids and Liver Disease. V. Endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G649 - G653. [Abstract] [Full Text] [PDF]

				A A Izzo and M Camilleri Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects Gut, August 1, 2008; 57(8): 1140 - 1155. [Abstract] [Full Text] [PDF]

				P. Pacher and B. Gao Endocannabinoids and Liver Disease. III. Endocannabinoid effects on immune cells: implications for inflammatory liver diseases Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G850 - G854. [Abstract] [Full Text] [PDF]

				S Moller and J H Henriksen Cardiovascular complications of cirrhosis Gut, February 1, 2008; 57(2): 268 - 278. [Abstract] [Full Text] [PDF]

				J. Munoz-Luque, J. Ros, G. Fernandez-Varo, S. Tugues, M. Morales-Ruiz, C. E. Alvarez, S. L. Friedman, V. Arroyo, and W. Jimenez Regression of Fibrosis after Chronic Stimulation of Cannabinoid CB2 Receptor in Cirrhotic Rats J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 475 - 483. [Abstract] [Full Text] [PDF]