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 cardioprotectio n and myocardial heat stress protein (HSP) expression. Moreover, heat stres s (HS), which also protects myocardium against ischaemic damages, is associ ated with a NO release. Therefore, we have investigated the implication of NO in MS-induced resistance to myocardial infarction, in the isolated rat h eart 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 no t 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 inh ibitor of the inducible NO synthase. Twenty-four hours after heat stress, t heir 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%) com pared to Sham (33.0 +/- 1.7%) hearts. This effect was abolished in L-NAME-t reated (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-NI L) 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, a ppear to play a role in the heat stress-induced cardioprotection, independe ntly of HSP 27 and 72 levels. Further investigations are required to elucid ate the precise role of HSPs in this adaptive response.