IGF-I REGULATION OF NA-K+-ATPASE IN RAT ARTERIAL SMOOTH-MUSCLE()

Insulin-like growth factor I (IGF-I) is vasodilatory and mitogenic for vascular smooth muscle cells (VSMC). Alteration in VSMC Na+-K+-adenos inetriphosphatase (Na+-K+-ATPase) activity is hypothesized to underlie abnormal vascular tone and growth in hypertension and diabetes. There fore, we investigated effects of IGF-I on Na+-K+-ATPase activity in ra t aortic VSMC. IGF-I increases pump activity in a dose- and time-depen dent 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 e ffects persisted through 12 h. In Na+-loaded cells, IGF-I does not fur ther 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 alpha(1)- and the alpha(2)-subunits of the pump were unaffected by IGF-I. Plasma mem brane 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 trans cription, protein synthesis, nitric oxide synthase activity, or protei n kinase C activity mediated this IGF-I effect. Therefore, IGF-I regul ates Na pump activity in the short term by an Na+/H+ exchange-dependen t but transcription/translocation-independent mechanism. These data su ggest that IGF-I, known to be produced by VSMC, may regulate tone and growth responses abnormal in disease states such as hypertension and d iabetes.