IGF-I regulation of Na+-K+-ATPase in rat arterial smooth muscle

Paul R. Standley, Feng Zhang, Ricardo M. Zayas, Ranganath Muniyappa, Mary F. Walsh, Edward Cragoe, James R. Sowers

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Insulin-like growth factor I (IGF-I) is vasodilatory and mitogenic for vascular smooth muscle cells (VSMC). Alteration in VSMC Na+-K+- adenosinetriphosphatase (Na+-K+-ATPase) activity is hypothesized to underlie abnormal vascular tone and growth in hypertension and diabetes. Therefore, we investigated effects of IGF-I on Na+-K+-ATPase activity in rat aortic VSMC. IGF-I increases pump activity in a dose- and time-dependent manner: the minimal dose required was 10-10 M, and the minimal time required was 20 min (at 10-8 M) to increase activity. Similar effects persisted through 12 h. In Na+-loaded cells, IGF-I does not further stimulate activity. Blockade of Na+/H+ exchange attenuates IGF-I-induced increases in activity after 30 min but has no effect after 12 h. Northern blot analyses reveal that expression of the α1- and the α2-subunits of the pump were unaffected by IGF-I. Plasma membrane α1- and α2-protein were also unaffected, suggesting translocation of preformed pools was not responsible for the increases. Inhibitors revealed that neither tyrosine kinase activity, RNA transcription, protein synthesis, nitric oxide synthase activity, or protein kinase C activity mediated this IGF-I effect. Therefore, IGF-I regulates Na pump activity in the short term by an Na+/H+ exchange- dependent but transcription/translocation-independent mechanism. These data suggest that IGF-I known to be produced by VSMC, may regulate tone and growth responses abnormal in disease states such as hypertension and diabetes.

Original languageEnglish (US)
Pages (from-to)E113-E121
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume273
Issue number1 36-1
StatePublished - Jul 1 1997
Externally publishedYes

Keywords

  • Hypertension
  • Insulin-like growth factor
  • Sodium-potassium- adenosinetriphosphatase
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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    Standley, P. R., Zhang, F., Zayas, R. M., Muniyappa, R., Walsh, M. F., Cragoe, E., & Sowers, J. R. (1997). IGF-I regulation of Na+-K+-ATPase in rat arterial smooth muscle. American Journal of Physiology - Endocrinology and Metabolism, 273(1 36-1), E113-E121.