Acetaldehyde dehydrogenase-2 activation inhibits myocardial ischemia-reperfusion injury in nitroglycerin tolerant rats

AIM:To investigate the effect of acetaldehyde dehydrogenase 2 (ALDH2) agonist (Alda-1) on the myocardial ischemia-reperfusion (MI/R) injury in nitroglycerin tolerant rats. METHODS: Male Sprague Dawley (SD) rats were randomized into control group (Con), Alda-1 group (Ald), nitroglycerin tolerant group (NTG) and Alda-1 treated NTG group (NTG+Ald). Rats were treated with NTG for 7 days ［10 mg/(kg·day) i.v.］ to establish the nitroglycerin tolerance model and the rats in treatment group were given Alda-1 ［3 days, 10 mg/(kg·day)］ concomitantly with NTG from the fifth day. The left anterior descending artery (LAD) was occluded for 30 min prior to 4 h reperfusion to establish the rat acute MI/R model. At the end of the 4-h reperfusion period, ALDH2 activities, reactive oxygen species (ROS) production, and myocardial protein carbonyl levels were measured and compared. RESULTS: Rats treated with NTG for 7 days caused marked tolerance as evidenced by impaired endothelium-dependent and -independent relaxation of aortic segments. Alda-1 treatment significantly improved cardiac ALDH2 activity under nitroglycerin tolerance. Compared with that of the control hearts, MI/R injury was significantly enhanced in NTG hearts as evidenced by reduced ±LVdP/dtmax, increased serum lactate dehydrogenase (LDH) and accentuated infarct size (P<0.05). ALDH2 activator infusion effectively suppressed the above mentioned ischemic injury in the NTG hearts (P<0.05). Alda-1 treatment significantly inhibited myocardial protein carbonylation and the content of ROS during MI/R in nitroglycerin tolerant animals. CONCLUSIONS: Activating myocardial ALDH2 can significantly inhibit the MI/R injury accentuation caused by nitroglycerin tolerance and the cardioprotection of ALDH2 may partially mediate through inhibiting cardiac protein oxidative damage.