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

David F. Gray, Henning Bundgaard, Peter S. Hansen, Kerrie A. Buhagiar, Anastasia S. Mihailidou, Wendy Jessup, Keld Kjeldsen, Helge H. Rasmussen*

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review


    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. (C) 2000 Elsevier Science B.V.

    Sider (fra-til)329-335
    Antal sider7
    TidsskriftCardiovascular Research
    Udgave nummer2
    StatusUdgivet - 1 aug. 2000


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