Abstract 1569: Postconditioning Exerts an Antiapoptotic Effect following Myocardial Ischemia-Reperfusion by Inhibiting iNOS Activity and Peroxynitrite (ONOO−) Production
Postconditioning has been reported to exert a significant anti-apoptotic effect against MI/R injury. However, its mechanism remains largely unknown. This study was designed to elucidate the signaling pathway involved in the anti-apoptotic effect of postconditioning in vivo. Male SD rats were subjected to 40 minutes of myocardial ischemia and 4 hours of reperfusion. Rats were randomized to receive vehicle, postconditioning( three cycles of 10 s reperfusion and 10 s LAD re-occlusion preceded the reperfusion),1400 W(10 μmol·kg−1·h−1, a selective iNOS hibitor), or postconditioning plus SIN-1(1 mmol·kg−1·h−, a ONOO− donor) (n=16). Myocardial apoptosis (TUNEL), nitrotyrosine (an ONOO− marker) and iNOS activity were determined. Compared with vehicle rats, postconditioning and 1400 W exerted a significant anti-apoptotic effect (postconditioning and 1400 W: 12.3±2.5 %, and 13.3±2.4%, vehicle: 18.1±2.2%, P<<med>0.01). There was no significant difference between postconditioning and 1400 W. SIN-1 reversed the anti-apoptotic effect of postconditioning (19.3±2.1%, P>0.5 vs. vehicle). Treatment with postconditioning resulted in a significant decrease in ONOO− production and iNOS activity in ischemic/reperfused myocardial tissue. 1400 W exerted the similar effects as postconditioning. The effect of postconditioning on ONOO− production was completely blocked by SIN-1, however, SIN-1 didn’t exert any significant effect on iNOS activity (Table 1⇓). Our results demonstrated that postconditioning reduced postischemic myocardial apoptosis partially by inhibiting iNOS activity and blocking ONOO− formation.