HMG CoA reductase inhibition reduces sarcolemmal Na(+)-K(+) pump density.
Cardiovasc Res
; 47(2): 329-35, 2000 Aug.
Article
em En
| MEDLINE
| ID: mdl-10946069
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcolema
/
Lovastatina
/
ATPase Trocadora de Sódio-Potássio
/
Inibidores de Hidroximetilglutaril-CoA Redutases
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Austrália