Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide.
We have examined the involvement of the endocannabinoid system in the cardioprotection triggered by lipopolysaccharide (LPS). Rats were treated with saline or LPS (10 microg x Kg(-1)). 24 h later, hearts were excised, retrogradely perfused, submitted to a low-flow ischaemia (0.6 ml x min(-1)) for 90 min and reperfused for 60 min. Some hearts were perfused with either SR 141716A (a cannabinoid CB(1), receptor antagonist 1 microM), SR 144528 (a CB2 receptor anagonist microM), NNLA (3 microM) or sodium nitroprusside (1 microM) 5 min before ischaemia and during the ischaemic period. The cardioprotective effects of LPS treatment, in terms of infarction and functional recovery, were not altered by the perfusion of SR 141716A but abolished by both SR 144528 and NNLA. Finally, SR 144528 abolished the beneficial effects of SNP perfusion. Our results suggest an involvement of endocannabinoids, acting through the CB2 receptors, in the cardioprotection triggered by LPS against myocardial ischaemia. This could be attributed to a relationship between cannabinoids and NO.
Lagneux
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Faculté de Pharmacie, Université de Montréal, CP 6128, Succursale centre ville, Montréal, Québec, Canada, H3C 3J7.
Lamontagne
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D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009569:Nitric Oxide / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology*; D000077285:Rimonabant
D001892:Camphanes; D063385:Cannabinoid Receptor Modulators; C469526:Cnr2 protein, rat; D008070:Lipopolysaccharides; D010880:Piperidines; D020011:Protective Agents; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D009569:Nitric Oxide; D000077285:Rimonabant