Digoxin and membrane sodium potassium ATPase inhibition in cardiovascular disease

Kerala has a high incidence of mucoid angiopathy, metabolic syndrome X and endomyocardial fibrosis. Magnesium deficiency has been reported in these disorders even though the Keralite diet has adequate magnesium. A possible cause of magnesium deficiency is the increased digoxin, a potent inhibitor membrane Na(+)-K+ ATPase which can lead to magnesium depletion. Digoxin is known to be synthesised by the hypothalamus and other tissues and can also be obtained from plant sources in the diet. Inhibition of Na(+)-K+ ATPase can cause intracellular magnesium depletion and increase in intracellular calcium. In view of these, a study has been carried out on the activity of membrane Na(+)-K+ ATPase, using RBC membrane, serum digoxin, magnesium and glycosaminoglycan levels in patients of mucoid angiopathy, endomyocardial fibrosis and syndrome X. Significant decrease in the membrane Na(+)-K+ ATPase was observed in patients while serum digoxin levels showed an increase. Serum magnesium was significantly lower while glycosaminoglycan levels were increased. The inhibition of Na(+)-K+ ATPase activity may be due to increase in endogenous and/or exogenous digoxin. This inhibition leads to depletion of intracellular magnesium and an increase in intracellular calcium load. The role of underlying magnesium-related insulin resistance and the consequence of this intracellular magnesium and calcium alteration in the pathogenesis of these disorders is discussed.