Document Detail

2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts.
MedLine Citation:
PMID:  16775503     Owner:  NLM     Status:  MEDLINE    
Endocannabinoids have been implicated in protective effects in the heart and brain, but the mechanism of possible infarct-size-reducing effects remains controversial. Using a model of delayed preconditioning (PC), rats received the nitric oxide (NO) donor nitroglycerin (0.15 mg/h/kg) for 24 hours via transdermal application. Two days later, rat isolated perfused hearts were subjected to global, no-flow ischemia (20 min), and reperfusion (120 min). Cannabinoid receptor antagonists were given before no-flow throughout the protocol. Endocannabinoids were detected by liquid chromatography and mass spectrometry. NO-induced PC reduced the left ventricular infarct size from 40.9 +/- 3.9% to 27.5 +/- 3.8% (P < 0.05). Treatment with the specific CB1 cannabinoid receptor antagonist AM-251 (0.3 microM) prevented the protective effect of PC on infarct size (40.2 +/- 4.7%, P > 0.05 vs. controls). On the contrary, the specific CB2 receptor antagonist AM-630 (0.3 microM) did not alter infarct size (31.6 +/- 6.3%, P > 0.05 vs. PC alone). Recovery of left ventricular developed pressure and coronary flow was incomplete in control and NO-pretreated hearts and not consistently altered by cannabinoid receptor antagonists. PC increased the heart tissue content of the endocannabinoid 2-arachidonylglycerol (2-AG) from 4.6 +/- 1.0 nmol/g in controls to 12.0 +/- 2.1 nmol/g (P < 0.05). Tissue levels of the endocannabinoid arachidonylethanolamide (anandamide) remained unchanged (19.8 +/- 3.9 pmol/g vs. 19.5 +/- 4.8 pmol/g). 2-AG (1 microM) or its metabolically stable derivative noladinether (0.1 microM), given 30 minutes before ischemia/reperfusion in unpreconditioned hearts, mimicked the cardioprotective effects of PC and reduced infarct size. We conclude that delayed PC through transdermal nitroglycerin application increases the production of the endocannabinoid 2-AG which elicits protective effects against myocardial infarction via CB1 cannabinoid receptors which represents one new mechanism of NO-mediated PC.
Jens A Wagner; Marco Abesser; Judith Harvey-White; Georg Ertl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  47     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-06-15     Completed Date:  2006-11-06     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  650-5     Citation Subset:  IM    
Department of Internal Medicine 1, Center of Cardiovascular Medicine, University of Würzburg, Würzburg, Germany.
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MeSH Terms
Arachidonic Acids / metabolism,  pharmacology*
Blood Pressure / drug effects
Coronary Vessels / drug effects,  physiology
Endocannabinoids / metabolism
Glycerides / metabolism,  pharmacology*
Heart / physiopathology
Heart Rate / drug effects
Indoles / pharmacology
Ischemic Preconditioning, Myocardial*
Myocardial Infarction / prevention & control*
Myocardial Reperfusion Injury / physiopathology
Myocardium / metabolism
Nitric Oxide / metabolism
Nitric Oxide Donors / pharmacology
Nitroglycerin / pharmacology*
Piperidines / pharmacology
Polyunsaturated Alkamides
Pyrazoles / pharmacology
Rats, Wistar
Receptor, Cannabinoid, CB1 / agonists*,  antagonists & inhibitors
Receptor, Cannabinoid, CB2 / antagonists & inhibitors
Regional Blood Flow / drug effects
Reg. No./Substance:
0/AM 251; 0/Arachidonic Acids; 0/Cnr2 protein, rat; 0/Endocannabinoids; 0/Glycerides; 0/Indoles; 0/Nitric Oxide Donors; 0/Piperidines; 0/Polyunsaturated Alkamides; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 0/iodopravadoline; 10102-43-9/Nitric Oxide; 53847-30-6/2-arachidonylglycerol; 55-63-0/Nitroglycerin; 94421-68-8/anandamide

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