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AIM: To investigate the protective effect of calcium antagonists on anoxia/reoxygenation (A/R) injury of cardiomyocytes. METHODS: Primary-cultured cardiomyocytes were divided into four groups, namely A/R, A/R+nifedipine(Nif), A/R+ruthenium red(Ru)+heparin (Hep) and control groups. The following parameters were measured in all groups: intracellular calcium concentration ([Ca 2+ ]i), cardiac cell viability, ATP content, lactate dehydrogenase (LDH) activity in the medium, PKC and MAPK activity and -Leucine(-Leu) incorporation. RESULTS: In comparison with A/R group, A/R+nifedipine(Nif) and A/R+ruthenium red(Ru)+heparin (Hep) groups showed a marked decrease in [Ca 2+ ]i and LDH content, and a significant increase in cell viability ,ATP content, activity of PKC and MAPK and -Leu incorporation(P
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AIM: To investigate the effect of intracellular calcium free calcium ([Ca~(2+)]i) on zinic finger transcription factor (GATA_4) and fetal heart gene in cardiomyocytes. METHODS: Cardiomyocytes from fetal rat were cultured primarily. Angiotensin Ⅱ (Ang Ⅱ) and ryanodine (RY) were used to stimulate transmembrane calcium inflow and intracellular calcium release. Fura-2/AM ratio imagine analysis was applied to detect intracellular Ca~(2+) signal. Western blotting were used to measure calcineurin (CaN), nuclear activated T cell factor (NFAT_3), GATA_4 and ?-actin. RT-PCR was applied for observing ?-myosin heavy chain (?-MHC). RESULTS: AngⅡ and RY promoted intracellular free calcium concentration ([Ca~(2+)]i) in cardiomyocytes (P
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AIM: To investigate the contribution of angiotensin-converting enzyme inhibitor (ACEI) to the regulation of calpain system in infarcted myocardium. METHODS: Rat myocardial infarction (MI) model was established by permanent ligation of the left coronary artery. The treatment with the ACEI inhibitor rampril (1 mg?kg~-1 ?d~-1 ) was started 7 days prior to surgery. On day 1, 3, 7 and 14 after MI, protein levels of calpainⅠ, Ⅱ and calpastatin were determined in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricule. RESULTS: CalpainⅠprotein level was increased in IS 14 d post MI, whereas the protein level of calpainⅡ was maximally increased in LVFW 3 d post MI. Rampril decreased protein up-regulation of calpainⅠ and Ⅱ, and reduced infarct size and interstitial fibrosis. Calpastatin protein expression was not affected by ACEI. CONCLUSIONS: CalpainⅠ is involved in cardiac remodelling in the late and calpainⅡ contributes to cardiac tissue damage in the early phase of MI. The heart protective effect of ACEI may be related to the inhibition of calpain system in the pathogenesis of myocardial infarction.
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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.