Effects of m-nisoldipine on aortic calcium accumulation in rats with vascular calcium overload
Abstract
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 IU.kg-1, p.o.) 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, p.o., 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, p.o., 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.
Keywords:
METHODS: VCO was induced in Wistar rats by treatment with colecalciferol (Col, 400,000 IU.kg-1, p.o.) 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, p.o., 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, p.o., 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.