It is not known why alcohol ingestion poses a risk for development of
hypertension,
stroke and
sudden death. Of all drugs, which result in body depletion of
magnesium (Mg), alcohol is now known to be the most notorious cause of Mg-wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce
hypertension,
stroke, and
sudden death via its effects on intracellular free Mg2+ ([Mg2+]i), which in turn alter cellular and subcellular bioenergetics and promote
calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic
ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic
ethanol increases the reactivity of intact microvessels to
vasoconstrictors and results in decreased reactivity to
vasodilators. Chronic
ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P-NMR spectroscopy coupled with optical-backscatter reflectance spectroscopy revealed that acute
ethanol administration to rats results in dose-dependent deficits in
phosphocreatine (PCr), the [PCr]/[
ATP] ratio, intracellular pH (pHi),
oxyhemoglobin, and the mitochondrial level of oxidized
cytochrome oxidase aa3 concomitant with a rise in brain-blood volume and
inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that [Mg2+]i is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents
ethanol from inducing
stroke and prevents all of the adverse bioenergetic changes from taking place. Use of quantitative digital imaging microscopy, and
mag-fura-2, on single-cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration-dependent depletion of [Mg2+]i. These cellular deficits in [Mg2+]i seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and
ischemia. A role for
ethanol-induced alterations in [Mg2+]i should also be considered in the well-known behavioral actions of alcohol.