A study on protective mechanism of calcium channel blockade in the rat myocardial remodeling / 中国药理学通报

ABSTRACT

Aim To investigate the contribution of cardiac L-and L/T-type Ca~2+ channels in the calpain mediated myocardial damage following myocardial infarction(MI).Methods Rat MI model was established by permanent ligation of the left coronary artery, infarcted rats were orally treated with placebo, amlodipine(L-channel blockade, 4 mg?kg~-1 ?d~-1 ) or mibefradil(L/T-Channel blockade, 10 mg?kg~-1 ?d~-1 ) beginning 7 d before induction of myocardial infarction. Protein levels of u-calpain and m-calpain were measured 1,3,7 and 14 d post coronary occlusion in the noninfarcted and infarcted myocardium.Infarcted size,left ventricular dilation were determined in picrosirius red stained hearts.Results Myocardial infarction induced an up regulation of u-calpain protein and activity in the noninfarcted myocardium(maximum day 14 days post infarction), whereas protein and activity of m-calpain were increased in the infarcted myocardium 3 d post infarction. Amlodipine inhibited protein up-regulation of u-calpain and decreased left ventricular dilation and interventricular septal thickness. Mibefradil attenuated protein up regulation of m-calpain 14 days post infarction, reduced infarct size more obviously.Conclusions Infarction-induced cardiac hypertrophy was accompanied by an up-regulation of u-calpain, whereas m-calpain was up-regulated in the infarcted myocardium in the processing of cardiac infarcted pathogensisi. Cardiac L and L/T-type Ca~2+ channel blockade differentially reduced post infarction remodeling associated with selective inhibition of cardiac u-calpain and m-calpain, respectively.