The effects of diazoxide on myocardium function and the expressions of ERK and JNK in isolated spontaneous hypertension rat hearts / 中国应用生理学杂志

ABSTRACT

<p><b>AIM</b>To investigate the effect of diazoxide preconditioning and the role of ERK and JNK in cellular signaling during diazoxide preconditioning protection in isolated spontaneous hypertension rat (SHR) hearts.</p><p><b>METHODS</b>Hearts were isolated from male SHR rats, and perfused on a Langendorff apparatus. Five groups were considered (n = 6). Con after 40 min perfusion the hearts were submitted to 25 min ischemia followed by 30 min reperfusion. IP the hearts were preconditioned with 2 periods of 5 min ischemia and 10 min reperfusion prior to 25 min ischemia. DP the hearts were preconditioned with 2 periods of 10 min K-H solution with 50 micromol x L(-1) diazoxide and 5 min K-H solution reperfusion prior to 25 min ischemia. 5-HD perfuse with 100 micromol x L(-1) 5-HD (a special mitochondrial ATP sensitive potassium channel blocker) for 10 min followed by 30 min K-H solution perfusion before 25 min ischemia. 5-HD + DP 100 micromol x L(-1) 5-HD was given for 10 min before diazoxide preconditioning.</p><p><b>RESULTS</b>During reperfusion, comparing with Con group, the recoveries of left ventricle developed pressure (LVDP), + dP/dt(max), - dP/dt(max) and left ventricle end diastolic pressure (LVEDP) were improved in IP and DP groups (P < 0.01 vs Con). At the end of reperfusion, compared with Con group, the expression of ERK in myocardium were higher in IP and DP groups (P < 0.01 vs Con), there was no significance between 5-HD and Con group, but 5-HD couldn't inhibit the expression of ERK induced by diazoxide preconditioning. The expression of JNK in IP and DP groups were decreased (P < 0.05 vs Con), this effect could been inhibited by 5-HD.</p><p><b>CONCLUSION</b>These results indicated that diazoxide preconditioning could mimic ischemic preconditioning, the activation of ERK expression and the declining of JNK expression involved in diazoxide preconditioning in isolated SHR hearts.</p>