The role of the endocannabinoid system in cirrhotic cardiomyopathy

Abstract

Advanced liver cirrhosis is associated with hyperdynamic circulation: hypotension, decreased peripheral resistance and cardiac dysfunction termed cirrhotic cardiomyopathy. Previous studies have revealed the role of endocannabinoids and CB1 receptors in the development of generalized hypotension in models of liver cirrhosis, and CB1 receptors have been also implicated in the decreased β‐adrenergic responsiveness of cirrhotic heart tissue. 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 low blood pressure, tachycardia and decreased cardiac contractility. CB1 antagonist AM251 acutely increased blood pressure as well as both load‐dependent and ‐independent indices of systolic function, whereas no such changes were elicited by AM251 in controls. Furthermore, tissue levels of the endocannabinoid anandamide increased in the heart of cirrhotic compared to control rats without any change in 2‐AG levels. CB1 receptor expression in the heart was unaffected by cirrhosis. Thus, 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.