Selective inhibition of p38  MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury (original) (raw)

2006, AJP: Heart and Circulatory Physiology

p38 MAPK is activated during heart diseases that might associate with myocardial damage and deterioration of cardiac function. In a rat model of myocardial injury, we have investigated cardioprotective effects of the inhibition of p38 MAPK using a novel, orally available p38α MAPK inhibitor. Rats were treated with Nω-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg−1·day−1) in drinking water plus 1% salt for 14 days and ANG II (0.5 mg·kg−1·day−1) for 3 days. A selective p38α MAPK inhibitor, SD-282 (60 mg/kg), was administrated orally, twice a day for 4 days, starting 1 day before ANG II administration. The cardioprotective effects of p38α MAPK inhibition were evaluated by improvement of cardiac function, reduction of inflammatory cell infiltration, and cardiomyocyte apoptosis. SD-282 significantly improved cardiac function indicated by increasing stroke volume, cardiac output, ejection fraction, and stroke work and significantly decreasing arterial elastance. SD-282 also significantl...