COX-2: an in vivo evidence of its participation in heat stress-induced myocardial preconditioning

Heat stress (HS) is known to induce delayed protection against myocardial infarction. We have previously shown that inducible nitric oxide synthase (iNOS), was involved in mediating this form of preconditioning. Since iNOS and cyclooxygenase-2 (COX-2) are co-induced in various cell types, the goal of this study was to investigate whether COX-2 could also participate to the HS-induced cardioprotection.A total of 78 male Wistar rats, subjected to either heat stress (42 degrees C for 15 min) or sham anaesthesia were used for this study. Twenty-four hours later, they were treated or not with a selective COX-2 inhibitor, either celecoxib (3 mg kg(-1), i.p.) or NS-398 (5 mg kg(-1), i.p.), 30 min before being subjected to a 30-min occlusion of the left coronary artery followed by a 120-min reperfusion, in vivo. HS resulted in a marked increase in myocardial COX-2 protein expression at 24 h, associated with a significant protection against infarction (46.0+/-1.4% in sham vs. 26.8+/-3.8% in HS group) (Por=0.05). Administration of selective COX-2 inhibitor 24 h after HS, completely abrogated this delayed cardioprotection (46.4+/-3.6 and 48.0+/-2.8%, respectively, in HS+celecoxib and HS+NS-398 groups).This study provides the first evidence of an implication of COX-2 as a mediator of HS-induced cardioprotection. This suggests that prostaglandins are involved in this type of cardioprotective preconditioning.