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

JACC: Basic to Translational Science

Volume 4, Issue 5, September 2019 DOI: 10.1016/j.jacbts.2019.05.007

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 and Pal Pacher

Author + information

vol. 4 no. 5 625-637

DOI:

https://doi.org/10.1016/j.jacbts.2019.05.007

Published By:

JACC: Basic to Translational Science

Online ISSN:

2452-302X

History:

Received March 20, 2019
Revision received May 4, 2019
Accepted May 13, 2019
Published online September 23, 2019.

Author Information

Janos Paloczi, PhD^a,
Csaba Matyas, MD, PhD^a,
Resat Cinar, PhD^b,
Zoltan V. Varga, MD, PhD^a,
György Hasko, MD, PhD^c,
Thomas H. Schindler, MD^d,
George Kunos, MD, PhD^b and
Pal Pacher, MD, PhD^a,^∗ (pacher{at}mail.nih.gov)

^aLaboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland
^bLaboratory of Physiological Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland
^cDepartment of Anesthesiology, Columbia University, New York, New York
^dDivision of Nuclear Medicine, Washington University in St. Louis, St. Louis, Missouri

↵∗Address for correspondence:
Dr. Pal Pacher, Laboratory of Cardiovascular Physiology and Tissue Injury, 5625 Fishers Lane, Room 2N-17, Bethesda, Maryland 20892-9413.

Visual Abstract

Highlights

• Alcohol is one of the most frequently used intoxicants in the United States. Binge alcohol drinking is a major contributor of emergency department visits.
• Binge alcohol drinking may adversely affect cardiovascular function.
• Here we show that acute alcohol intoxication is associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction and blood redistribution lasting for several hours.
• The adverse cardiovascular effects of acute alcohol intoxication are attenuated by CB1-R antagonist or in CB1-R knockout mice.
• A single alcohol binge has profound effect on the cardiovascular system, which involves endocannabinoid-CB1-R signaling.

Summary

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.

Key Words

Footnotes

This study was supported by the Intramural Research Program of NIH/NIAAA to Dr. Pacher. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.