Igf-1 regulation of na+,k+-atpase in rat arterial smooth
muscle.
Standley, Paul R., Feng Zhang, Ricardo M. Zayas, Ranganath Muniyappa,
Mary F. Walsh, Edward Cragoe, and James R. Sowers.
Departments of Medicine and Physiology, Wayne State University
School of Medicine and Veteran's Administration Medical Center,
Detroit, MI
APStracts 4:0070E, 1997.
IGF-1 is vasodilatory and mitogenic for vascular smooth muscle cells
(VSMC). Alteration in VSMC Na+,K+-ATPase activity is hypothesized to
underlie abnormal vascular tone and growth in hypertension and
diabetes. Therefore we investigated effects of IGF-1 on Na+,K+-ATPase
activity in rat aortic VSMC. IGF-1 increases pump activity in a dose-
and time-dependent manner: the minimal dose required was 10-10 M the
minimal time required was 20 min. (at 10-8 M) to increase activity.
Similar effects persisted through 12 hrs. In Na+-loaded cells, IGF-1
does not further stimulate activity. Blockade of Na+/H+ exchange
attenuates IGF-1-induced increases in activity after 30 mins, but has
no effect after 12 hrs. Northern blot analyses reveals that
expression of the [alpha]1 and the [alpha]2 subunits of the pump were
unaffected by IGF-1. Plasma membrane [alpha]1 and [alpha]2 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 nor protein kinase C activity mediated
this IGF-1 effect. Therefore, IGF-1 regulates Na pump activity in the
short term by a Na+/H+ exchange-dependent, but
transcription/translocation-independent mechanism. These data suggest
that IGF-1 --known to be produced by VSMC-- may regulate tone and
growth responses abnormal in disease states such as hypertension and
diabetes.
Received 18 September 1996; accepted in final form 26 February
1997.
APS Manuscript Number E467-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 3 April 1997