Effects of N-n-butyl haloperidol iodide on the rat myocardial sarcoplasmic reticulum Ca 2+ -ATPase during ischemia/reperfusion

Abstract We have previously shown that N - n -butyl haloperidol iodide (F 2 ), a newly synthesized compound, reduces ischemia/reperfusion (I/R) injury by preventing intracellular Ca 2+ overload through inhibiting L-type calcium channels and outward current of Na + /Ca 2+ exchanger. This study was to investigate the effects of F 2 on activity and protein expression of the rat myocardial sarcoplasmic reticulum Ca 2+ –ATPase (SERCA) during I/R to discover other molecular mechanisms by which F 2 maintains intracellular Ca 2+ homeostasis. In an in vivo rat model of myocardial I/R achieved by occluding coronary artery for 30–60 min followed by 0–120 min reperfusion, treatment with F 2 (0.25, 0.5, 1, 2 and 4 mg/kg, respectively) dose-dependently inhibited the I/R-induced decrease in SERCA activity. However, neither different durations of I/R nor different doses of F 2 altered the expression levels of myocardial SERCA2a protein. These results indicate that F 2 exerts cardioprotective effects against I/R injury by inhibiting I/R-mediated decrease in SERCA activity by a mechanism independent of SERCA2a protein levels modulation.