Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling

Janos Paloczi; Csaba Matyas; Resat Cinar; Zoltan V Varga; György Hasko; Thomas H Schindler; George Kunos; Pal Pacher

doi:10.1016/j.jacbts.2019.05.007

Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling

JACC Basic Transl Sci. 2019 Sep 23;4(5):625-637. doi: 10.1016/j.jacbts.2019.05.007. eCollection 2019 Sep.

Authors

Janos Paloczi¹, Csaba Matyas¹, Resat Cinar², Zoltan V Varga¹, György Hasko³, Thomas H Schindler⁴, George Kunos², Pal Pacher¹

Affiliations

¹ Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland.
² Laboratory of Physiological Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland.
³ Department of Anesthesiology, Columbia University, New York, New York.
⁴ Division of Nuclear Medicine, Washington University in St. Louis, St. Louis, Missouri.

Abstract

Excessive binge alcohol drinking may adversely affect cardiovascular function. In this study we characterize the detailed hemodynamic effects of an acute alcohol binge in mice using multiple approaches and investigate the role of the endocannabinoid-cannabinoid 1 receptor (CB1-R) signaling in these effects. Acute alcohol binge was associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction lasting for several hours and redistribution of circulation. These changes were attenuated by CB1-R antagonist or in CB1-R knockout mice. Our results suggest that a single alcohol binge has profound effects on the cardiovascular system, which involve endocannabinoid-CB1-R signaling.

Keywords: 2-AG, 2-arachidonyl glycerol; AEA, anandamide; CB1-R (CB1), cannabinoid 1 receptor; CB2-R (CB2), cannabinoid 2 receptor; EF, ejection fraction; LV, left ventricle; MAP, mean arterial pressure; P-V, pressure-volume; PRSW, preload recruitable stroke work; TPR, total peripheral resistance; binge alcohol drinking; cannabinoids; contractility; dP/dtmax, maximal slope of pressure increment; endocannabinoids.