间尼索地平对血管钙超负荷大鼠主动脉钙积累的作用(英文)

Effects of m -nisoldipine on aortic calcium accumulation in rats with vascular calcium overload

目的:在组织和细胞水平探讨间尼索地平(m-Nis)对血管钙超负荷(VCO)大鼠主动脉钙积累的作用。方法:建立大鼠VCO模型,用原子吸收分光光度法和电子探针微分析法分别测定主动脉总钙和动脉平滑肌亚细胞钙。结果:m-Nis(1—15mg·kg^(-1))对VCO大鼠主动脉总钙升高作用弱,且量效关系呈钟罩形。m-Nis 2.5mg·kg^(-1)对总钙升高抑制为24％。维拉帕米12.5mg·kg^(-1)疗效略优于m-Nis。m-Nis2.5mg·kg^(-1)对主动脉中膜平滑肌细胞的胞浆和线粒体钙升高有明显抑制,抑制率分别为72％和76％,对胞核钙升高抑制稍小。结论:m-Nis对VCO大鼠主动脉主要抑制血管平滑肌细胞内尤其是胞浆和线粒体钙超负荷,而对组织间质钙沉积作用较弱。

AIM: To study the effects of a novel calcium channel blocker, m-nisoldipine, on vascular calcium overload (VCO) at both tissue and cellular levels. METHODS: VCO was induced in Wistar rats by treatment with colecalciferol (Col, 400 000 ID· kg-1, po) and an aqueous mixture of ethanol and polyethyleneglycol-400 for 3 d. The tissue and subcellular calcium contents of aorta were determined by atomic absorption spectrometer and electron probe microanalysis, respectively. RESULTS: Chronic treatment with m-nisoldipine (m-Nis, 1 - 15 mg·kg-1, po, bid) only had mild inhibition on the elevation of total calcium in aorta, and the dose-response relationship of m-Nis displayed a bell shape, with inhibition ratio of 24 % only for m-Nis 2.5 mg · kg-1. The effect of verapamil (12.5 mg·kg-1, po, bid) was a little better than that of m-Nis. The intracellular VCO in medial smooth muscle cells of aorta were remarkably inhibited by m-Nis (2.5 mg·kg-1). with inhibition ratios of 72 % for cytoplasm and 76 % for mitochondrion. The calcium accumulation in nucleus was reduced to a lesser degree than those in cytoplasm and mitochondrion. CONCLUSION: As for aorta in VCO rats, m-Nis mainly had conspicuous inhibition on intracellular VCO in medial smooth muscle cells, particularly in cytoplasm and mitochondrion, but with little effect on extracellular calcium deposition at tissue level.