Ku D D, Ann H S
J Pharmacol Exp Ther. 1987 Jun;241(3):961-6.
In the present study, effects of magnesium deficiency on coronary vascular reactivity changes were studied in isolated canine coronary arteries before and after endothelium disruption. Lowering of extracellular magnesium produced a potent vasorelaxant response in coronary arteries with intact endothelium, whereas in arteries with disrupted endothelium a potent vasoconstrictory response was observed. The magnitude of magnesium deficiency-induced vasorelaxation is also dependent on the extracellular calcium concentrations, such that lowering of extracellular calcium from 1.75 to 0.22 mM completely abolished the magnesium deficiency-induced vasorelaxant effects. Similar inhibition, as well as reversal, of magnesium deficiency-induced vasorelaxation was also observed with dichlorobenzamil, a known inhibitor of the Na+/Ca++ exchange mechanism, but not with nifedipine, a known inhibitor of the voltage-operated calcium channel. The magnesium deficiency-induced vasoconstriction, on the other hand, is endothelium-independent. Although a similar dependency on extracellular calcium concentration was observed in this vasoconstrictory response, nifedipine, but not dichlorobenzamil, was found to be effective in inhibiting the vasoconstrictory effect. Hemoglobin, a known inhibitor of the endothelium-derived relaxing factor, also completely inhibited the magnesium deficiency-induced vasorelaxation but had no effect on the latter vasoconstrictory effect. These results suggest that circulating magnesium ion may have a dual effect in the modulation of coronary vascular reactivity. In coronary vessels with intact endothelium, lowering of extracellular magnesium may potentiate calcium-induced basal release of endothelium-derived relaxing factor and result in vasodilation, whereas in pathological vessels with injured endothelial cells, a similar lowering of magnesium may increase coronary vascular tone by accentuating the calcium-induced coronary constrictory response in vascular smooth muscle cells and result in vasoconstriction.
在本研究中，我们研究了镁缺乏对犬离体冠状动脉内皮破坏前后冠状动脉血管反应性变化的影响。细胞外镁浓度降低会使内皮完整的冠状动脉产生强烈的血管舒张反应，而在内皮破坏的动脉中则观察到强烈的血管收缩反应。镁缺乏诱导的血管舒张程度也取决于细胞外钙浓度，当细胞外钙浓度从1.75 mM降至0.22 mM时，镁缺乏诱导的血管舒张作用完全消失。用已知的Na+/Ca++交换机制抑制剂二氯苯甲酰胺也观察到了对镁缺乏诱导的血管舒张的类似抑制以及逆转作用，但用已知的电压门控钙通道抑制剂硝苯地平则未观察到这种作用。另一方面，镁缺乏诱导的血管收缩与内皮无关。虽然在这种血管收缩反应中也观察到了对细胞外钙浓度的类似依赖性，但发现硝苯地平而非二氯苯甲酰胺能有效抑制血管收缩作用。血红蛋白是一种已知的内皮源性舒张因子抑制剂，它也完全抑制了镁缺乏诱导的血管舒张，但对后者的血管收缩作用没有影响。这些结果表明，循环中的镁离子可能在调节冠状动脉血管反应性方面具有双重作用。在内皮完整的冠状动脉中，细胞外镁浓度降低可能会增强钙诱导的内皮源性舒张因子的基础释放并导致血管舒张，而在有内皮细胞损伤的病理血管中，类似的镁浓度降低可能会通过增强血管平滑肌细胞中钙诱导的冠状动脉收缩反应来增加冠状动脉血管张力并导致血管收缩。
