TY - JOUR
T1 - IGF-I regulation of Na+-K+-ATPase in rat arterial smooth muscle
AU - Standley, Paul R.
AU - Zhang, Feng
AU - Zayas, Ricardo M.
AU - Muniyappa, Ranganath
AU - Walsh, Mary F.
AU - Cragoe, Edward
AU - Sowers, James R.
PY - 1997/7
Y1 - 1997/7
N2 - 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.
AB - 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.
KW - Hypertension
KW - Insulin-like growth factor
KW - Sodium-potassium- adenosinetriphosphatase
KW - Vascular smooth muscle
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U2 - 10.1152/ajpendo.1997.273.1.e113
DO - 10.1152/ajpendo.1997.273.1.e113
M3 - Article
C2 - 9252487
AN - SCOPUS:0030767892
SN - 0193-1849
VL - 273
SP - E113-E121
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 1 36-1
ER -