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

D F Gray, H Bundgaard, P S Hansen, K A Buhagiar, A S Mihailidou, W Jessup, K Kjeldsen, H H Rasmussen

31 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftCardiovascular Research
Vol/bind47
Udgave nummer2
Sider (fra-til)329-35
Antal sider7
ISSN0008-6363
DOI
StatusUdgivet - aug. 2000
Udgivet eksterntJa

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