Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts

Objective: We have investigated the involvement of the endocannabinoid system in the delayed cardioprotection conferred by heat stress preconditioning in the isolated rat heart. Methods: Rats were divided into eight groups (n = 7 in each group), subjected to either heat stress (42 degreesC for 15 min, HS groups) or sham anaesthesia (Sham groups). Twenty-four hours later, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Some hearts were perfused with either SR 141716 (a cannabinoid CB1 receptor antagonist, 1 muM), SR 144528 (a CB2 receptor antagonist, 1 muM) or L-NAME (a NOS inhibitor, 3 muM) 5 min before ischaemia and during the ischaemic period. Results: The infarct size-reducing effect conferred by heat stress (35.7 +/- 1.8% in Sham to 14.1 +/- 0.6% in HS groups) was not altered by the perfusion of SR 141716 ( 11.2 +/- 1.5%) but was abolished by both SR 144528 (36.6 +/- 1.6%) and L-NAME (32.0 +/- 4.4%). In hearts from non-heat-stressed rats, perfusion with SR 141716 (32.8 +/- 1.6%), SR 144528 (33.4. +/- 2.2%) and L-NAME (31.6 +/- 2.9%) had no effect on infarct size. Conclusion: These results suggest an involvement of endocannabinoids, acting through CB2 receptors, and NO in the cardioprotection conferred by heat stress against myocardial ischaemia, The possible interaction between both mediators of the heat stress response remains to be determined. (C) 2002 Elsevier Science B.V. All rights reserved.