Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells:: possible relationship to [Ca2+]i, atherogenesis and stroke

Homocysteine (HC) at concentrations of from 0.05 to 1.0 mM caused dose-dependent loss of [Mg2+](i) in cultured cerebral vascular smooth muscle cells (VSMC), whereas cysteine and methionine (its metabolic products) failed to interfere with changes in [Mg2+](i). HC, methionine and cysteine did not produce any changes in [Ca2+](i). Lowering [Mg2+](o) to 0.3 mM resulted in elevation of [Ca2+](i) and loss of [Mg2+](i). Depletion of [Mg2+](i), induced by HC, was potentiated by low Mg2+ Preincubation of these cells with vitamin B-6, vitamin B-12, folic acid, alone, did not alter [Ca2+](i) or [Mg2+](i). Likewise, concomitant addition of vitamin B-6, vitamin B-12, or folic acid, together with HC (1 mM) did not change the reduction in [Mg2+](i) induced by HC. However, concomitant addition of HC and the three vitamins inhibited completely the loss of [Mg2+](i). Exposure of these cells to each vitamin, alone, or combination of the three vitamins failed to interfere with reduction in [Mg2+](i) induced by low [Mg2+](i), but it did suppress the rise in [Ca2+](i). Interestingly, in the presence of low [Mg2+](o), the vitamin combination did not retard depletion of [Mg2+](i). The present findings are compa tible with the hypothesis that an increased serum HC concentration causes abnormal metabolism of Mg2+ in cerebral VSMC, thus priming these cells for HC-induced atherogenesis, cerebral vasospasm and stroke. Our results suggest the need for the three B-vitamins, together with normal physiological levels of Mg2+, in order to prevent [Mg2+](i) depletion and occlusive cerebral vascular diseases induced by homocysteinemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.