Endothelin‐1 blockade with bosentan attenuates15‐F2t‐Isoprostane adverse effects on postischemic rat hearts

15‐F2t‐Isoprostane (IsoP), a specific marker of oxidative stress, is increased after myocardial ischemia. It exerts deleterious effects on postischemic myocardium. We hypothesized that IsoP exacerbates post‐ischemic myocardial injury by stimulating endothelin‐1 (ET‐1) production. Adult rat hearts were perfused by the Langendorff technique. Global myocardial ischemia was induced by stopping perfusion for 40 min followed by 60 min of reperfusion. Hearts were randomized to one of five groups: untreated (C), treated with IsoP (100 nM) or the ET‐1 receptor A/B antagonist bosentan (1 μM) alone or in combination 10 min prior to ischemia and for 15 min during reperfusion or treated with IsoP as above plus delayed bosentan administration 15 min after reperfusion. Coronary effluent ET‐1 levels in the IsoP group were higher than those in the C group during reperfusion accompanied with increased release of cardiac‐specific creatine kinase, reduced cardiac contractility and increased myocardial infarct size (all p<0.05 vs. C). Bosentan administration during early reperfusion exacerbated the IsoP deleterious effects while delayed administration attenuated it. It is concluded that IsoP‐induced ET‐1 production during later reperfusion is detrimental to functional recovery of damaged myocardium while ET‐1 increase during early reperfusion seems to improve it. Supported by NSFC grants (30872447 and 30672003)