Hypophosphatemia and hypomagnesemia result in cardiovascular dysfunction: theoretical basis for alcohol-induced cellular injury.
Although it has been known for many years that prolonged ingestion of ethanol may be associated with numerous side effects, among them cardiovascular alterations, e.g., hypertension, cardiac arrhythmias, strokes, and cardiomyopathy, a direct cause and effect between alcohol and injury to the cardiovascular system has only been accepted recently. However, what mechanism is responsible for these cardiovascular alterations remains to be determined. Since it is well known that chronic alcohol consumption leads to hypophosphatemia and hypomagnesemia, we designed experiments to determine if controlled depletion of either phosphorous or magnesium (Mg2+) lead, in themselves, to cardiovascular disturbances and what effects these mineral depletions exert on myocardial cellular bioenergetics. Biochemical studies were carried out on left ventricular muscle, including mitochondrial and myofibrillar preparations. With respect to phosphate depletion, myocardial creatine phosphate, ATP, and ADP levels were reduced. Phosphate depletion also reduced mitochondrial and myofibrillar creatine phosphokinase activities; significant alterations in mitochondrial oxygen consumption, acid-extractable phospholipid precursors, and mitochondrial oxidation of long chain fatty acids were noted. With respect to magnesium depletion, significant reductions in inorganic oxygen consumption was also reduced. Utilizing these data, we have proposed several schemes for possible alcoholic-induced myocardial and vascular injury.
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000378:metabolism; D008275:Magnesium Deficiency / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D010101:Oxygen Consumption; D010758:Phosphorus / Q000172:deficiency*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010758:Phosphorus; D000431:Ethanol; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase