title: Magnesium deficiency produces endothelium-dependent vasorelaxation in canine coronary arteries.
abstract: 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.
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D008275:Magnesium Deficiency / Q000503:physiopathology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D014664:Vasodilation
chemical_list: C041470:3',4'-dichlorobenzamil; D000584:Amiloride; D009543:Nifedipine