To investigate the involvement of reperfusion-induced salvage kinases (RISK) as possible signaling molecules for the cardioprotective effects of BMS-180448, a prototype mitochondrial ATP-sensitive K$^*$ (mitoK$_{ATP}$ ) channel opener, we measured its cardioprotective effects in a rat model of jschemia/reperfusion (1/R) heart injury, together with western blotting analysis of five different signaling proteins. in isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, BMS-180448 (1, 3 and 10 K${mu}$M) significantly increased reperfusion left ventricular developed pressure (LVDP) and 30-min reperfusion double product (heart rate x LVDP) in a concentration-dependent manner, while decreasing left ventricular end-diastolic pressure (LVEDP) throughout reperfusion period in a concentration-dependent manner. SDS-PAGE/western blotting analysis of left ventricle reperfused for 30 min revealed that BMS-180448 significantly decreased phospho-GSK3K${eta}$ at high concentration, whereas it tended toincrease slightly phospho-eNOS and phospho-p70S6K with concentration. However, BMS-180448 had re effect on phospho-Akt and phospho-Bad. These results suggest that the car-dioprotective effects of BMS-180448 against 1/R heart injury may result from direct activation of mitoK$_{ATP}$ channel in cardiomyocytes, with the minimal role of RISK pathway in the activation of this channel and the cardioprotective effects of BMS-180448.