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Cardiovascular Research 2000 47(2):329-335; doi:10.1016/S0008-6363(00)00106-1
© 2000 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

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

David F Graya,b, Henning Bundgaardc, Peter S Hansena,b, Kerrie A Buhagiara,b, Anastasia S Mihailidoua, Wendy Jessupd, Keld Kjeldsenc and Helge H Rasmussena,b,*

aDepartment of Cardiology, Royal North Shore Hospital, Sydney, Australia
bThe University of Sydney, Sydney, Australia
cDepartment of Medicine, The Heart Centre, Rigshospitalet, National University Hospital, Copenhagen, Denmark
dThe Heart Research Institute, Sydney, Australia

* Corresponding author. Tel.: +61-2-9926-8680; fax: +61-2-9926-6521 helger{at}med.usyd.edu.au

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 (Ip) 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 Ip, myocardial and skeletal muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and skeletal muscle. The lovastatin-induced decrease in Ip 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.

KEYWORDS Cell culture/isolation; Cholesterol; Lipid metabolism; Membrane transport; Na/K-Pump


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