Cited by 219Cannabis and Cannabinoid ResearchCardiac Ischemia and ReperfusionOrgan Transplantation Techniques and Outcomes

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Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning.

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Pacher, P, Haskó, G·2008·British Journal of Pharmacology

DOI 10.1038/sj.bjp.0707582PMC PMC2219536

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Abstract

Ischaemia-reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB1/CB2 receptor-dependent and -independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB1 receptor agonists or knockout mice demonstrated CB1 receptor-dependent protection against cerebral I/R injury in various animal models. In contrast, several follow-up reports have shown protection afforded by CB1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB2 receptor agonists and/or knockout mice have provided compelling evidence that CB2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage.

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Authors: Pacher, P., & Haskó, G.
Affiliations: National Institutes of Health (US)
Rutgers New Jersey Medical School (US)
Corresponding author: Pacher, P
ORCID: Pacher, P
Venue: British Journal of Pharmacology
Publisher: Wiley
Published: 2008-01
Volume: 153
Issue: 2
Pages: 252-262
ISSN: 0007-1188 (ISSN-L)
1476-5381
DOI: 10.1038/sj.bjp.0707582
PMC: PMC2219536
OpenAlex: W2027688921
Cited by: 217
References: 132
Citations by year: 2026: 3 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 12 · 2012: 14
FWCI: 2.13
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 394 d)
Locations: British Journal of Pharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (Z99‐AA999999)
National Institute on Alcohol Abuse and Alcoholism (Z01AA000375)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords: endocannabinoids, cannabinoid receptors, CB1 receptor, CB2 receptor, ischemia-reperfusion injury, ischemic preconditioning, myocardial infarction, cerebral ischemia, hepatic ischemia, shock, CB2 receptor agonist, endothelial activation, inflammation, leukocyte transendothelial migration, oxidative stress, neuroprotection
MeSH terms: Animals, Humans, Liver Diseases, Shock, Reperfusion Injury, Myocardial Reperfusion Injury, Ischemic Preconditioning, Stroke, Receptors, Cannabinoid, Cannabinoid Receptor Modulators, Cannabinoid Receptor Agonists, Endocannabinoids

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Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning.

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