HMG CoA reductase inhibition reduces sarcolemmal Na+–K+ pump density

OBJECTIVES: HMG CoA reductase inhibitors reduce cellular availability of mevalonate, a precursor in cholesterol synthesis. Since the cholesterol content of cell membranes is an important determinant of Na(+)-K(+) pump function we speculated that treatment with HMG CoA reductase inhibitors affects Na(+)-K(+) pump activity. METHODS: We treated rabbits and rats for 2 weeks with the HMG CoA reductase inhibitor lovastatin and measured Na(+)-K(+) pump current (I(p)) in isolated rabbit cardiac myocytes using the whole cell patch-clamp technique, K-dependent p-nitrophenyl phosphatase (p-NPPase) activity in crude myocardial and skeletal muscle homogenates, and vanadate-facilitated 3H-ouabain binding in intact skeletal muscle samples from rats. RESULTS: Treatment with lovastatin caused statistically significant reductions in I(p), myocardial and skeletal muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and skeletal muscle. The lovastatin-induced decrease in I(p) was eliminated by parenteral co-administration of mevalonate. However, this was not related to cardiac cholesterol content. CONCLUSIONS: Treatment with lovastatin reduces Na(+)-K(+) pump activity and abundance in rabbit and rat sarcolemma.