Long-term diazoxide preconditioning attenuates the cardioprotective effect against isoproterenol induced myocardial injury in a rat model

Abstract

Short-term diazoxide (DZ) preconditioning exerts efficient protective effect on myocardial ischemia injury. This study aimed to investigate the effects of long term DZ preconditioning on isoproterenol (ISO) induced myocardial injury. DZ (20 mg/kg/d) was intraperitoneally injected into rats for different durations (1, 2, 4, 6 and 8 w) and myocardial injury was then introduced through intraperitoneal injection of ISO. The mitochondrial respiratory function and the cardiac troponin(cTnI) level in the blood were measured. In addition, the mRNA and protein expressions of SUR2A were detected. After DZ preconditioning for 1~4 w, the myocardial protective effect was observed in this ISO induced myocardial injury model and was similar to that after 3 days of DZ preconditioning. After DZ preconditioning for 6 to 8 w, the protective effect was markedly attenuated, characterized by impaired mitochondrial respiratory function and increased blood cTnI level. Furthermore, qRT-PCR and western blot assay revealed no significant difference in the mRNA and protein expressions of SUR2A among groups. Long term DZ preconditioning (≥6 w) may attenuate the protective effect against the ISO-induced myocardial injury, which might be associated with the persistent opening of mitochondrial ATP-sensitive potassium channel. Key words: Diazoxide preconditioning, isoproterenol-induced myocardial injury, mitochondrial adenosine triphosphate -sensitive potassium channel.