Role of nitric oxide syntheses in the infarct size-reducing effect conferred by heat stress in isolated rat hearts

1 Nitric oxide (NO) donors are known to induce both delayed cardioprotection and myocardial heat stress protein (HSP) expression. Moreover, heat stress (HS), which also protects myocardium against ischaemic damages, is associated with a NO release. Therefore, we have investigated the implication of NO in MS-induced resistance to myocardial infarction, in the isolated rat heart model. 2 Rats were divided in six groups (n = 10 in each group), subjected or not to heat stress (42 degreesC internal temperature, 15 min) and treated or not with nitro-L-arginine-methylester (L-NAME) a nonselective inhibitor of NO synthase isoforms, or L-N-6-(1-imino-ethyl)lysine (L-NIL), a selective inhibitor of the inducible NO synthase. Twenty-four hours after heat stress, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. 3 Infarct-to-risk ratio was significantly reduced in HS (18.7 +/- 1.6%) compared to Sham (33.0 +/- 1.7%) hearts. This effect was abolished in L-NAME-treated (41.7 +/- 3.1% in HS + L-NAME vs 35.2 +/- 3.0% in Sham + L-NAME) and L-NIL-treated (36.1 +/- 3.4% in HS + L-NIL vs 42.1 +/- 4.6% in Sham + L-NIL) groups. Immunohistochemical analysis of myocardiaI HSP 27 and 72 showed an MS-induced increase of these proteins, which was not modified by L-NAME pretreatment. 4 We conclude that NO synthases, and in particular the inducible isoform, appear to play a role in the heat stress-induced cardioprotection, independently of HSP 27 and 72 levels. Further investigations are required to elucidate the precise role of HSPs in this adaptive response.