Antioxidants prevent elevation in [Ca 2+] i induced by low extracellular magnesium in cultured canine cerebral vascular smooth muscle cells: possible relationship to Mg 2+ deficiency-induced vasospasm and stroke

Abstract

Low serum concentrations of Mg 2+ ions have been reported, recently, in patients with coronary disease, atherosclerosis and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [α-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Ca 2+ ([Ca 2+] i) overload associated with cerebral vascular injury induced by low extracellular free Mg 2+ ([Mg 2+] o). Exposure of cultured canine cerebral vascular smooth muscle cells to low [Mg 2+] o (0.15–0.6 mM) vs. normal [Mg 2+] o (1.2 mM) for either 10 min or 2 h induced concentration-dependent rises in [Ca 2+] i. Treatment of the cultured cells with either PDTC (0.1 μM) or α-tocopherol (15 μM) for 24 h, alone, failed to interfere with basal [Ca 2+] i levels. However, preincubation of the cells with either α-tocopherol or PDTC for 24 h completely inhibited the elevation of [Ca 2+] i induced by exposure to low [Mg 2+] o, not only for 10 min, but also for 2 h. These results indicate that α-tocopherol and PDTC prevent rises in [Ca 2+] i produced by low [Mg 2+] o, which probably result from low [Mg 2+] o-induced lipid peroxidation of cerebral vascular smooth muscle cell membranes. Moreover, these new results suggest that such protective effects of α-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in cerebral vascular injury associated with low [Mg 2+] o and accumulation of [Ca 2+] i.