ALCOHOL-INDUCED VASCULAR DAMAGE OF BRAIN IS AMELIORATED BY ADMINISTRATION OF MAGNESIUM

Ethanol ingestion can cause irreversible neuronal and Vascular damage in the brain and stroke-like events. Using an intact in vivo rat brain (pial) model, TV image-intensification, cultured cerebral vascular mu scle cells, digital-image analysis, and a novel Mg2+ ion;selective ele ctrode to measure extracellular ionized Mg2+, studies were designed to determine whether: 1) perivascular or systemic administration (IV or intra-arterial) of magnesium aspartate HCl (MgA) exert vasodilator eff ects on arterioles (65-130 mu m o.d.) and venules (60-135 mu m); 2) no nvasodilator doses of MgA could modify vascular spasms induced by BaCl 2 and ethanol; 3) nonvasodilator doses of MgA could ameliorate or prev ent the cerebral vascular damage induced by high doses of ethanol; and 4) ethanol depletes cerebral vascular muscle of intracellular Mg ions ([Mg2+](i)). Perivascular application of MgA (0.01-100 mu mol) produc ed dose-dependent vasodilatation of cerebral arterioles and venules; a rterioles yielded greater vasodilator responses compared to venules. N onvasodilator doses of Mg (1.0, 4.0 mu mol/min), administered IV or in tra-arterially, into a branch of the internal carotid artery, prevente d: I)the spasmogenic actions of ethanol and Ba2+; and 2) the vasculoto xic actions (rupture of postcapillary venules and focal hemorrhages) o f ethanol. In addition, ethanol depleted cerebral vascular muscle cell s of [Mg2+](i); blood levels of ionized Mg2+ rose after IP ethanol. De spite the fact that systemic! infusion of low nonvasodilator doses did not result in dilatation of the pial arterioles and venules,plasma to tal and ionized Mg rose 18-230%, depending upon dose of MgA and time o f plasma sampling. These data support the idea that Mg2+ can act as a local vasodilator on brain microvessels and possess antispasmodic prop erties on brain arterioles and venules. In addition, our results indic ate that Mg may possess Some unique cerebral vascular protective prope rties against the vasculotoxic effects of ethanol. Lastly, these findi ngs suggest ethanol-induced cerebrovasospasm and vascular damage appea r to be associated with a rapid loss of [Mg2+](i) from cerebral vascul ar muscle cells. (C) 1998 Elsevier Science Inc.