Standley P R, Zhang F, Zayas R M, Muniyappa R, Walsh M F, Cragoe E, Sowers J R
Department of Physiology, Midwestern University, Glendale, Arizona 85308, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):E113-21. doi: 10.1152/ajpendo.1997.273.1.E113.
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 alpha 1- and the alpha 2-subunits of the pump were unaffected by IGF-I. 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, 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.
胰岛素样生长因子I（IGF-I）对血管平滑肌细胞（VSMC）具有血管舒张和促有丝分裂作用。血管平滑肌细胞钠钾-腺苷三磷酸酶（Na(+)-K(+)-ATPase）活性的改变被认为是高血压和糖尿病中血管张力异常和生长异常的基础。因此，我们研究了IGF-I对大鼠主动脉血管平滑肌细胞Na(+)-K(+)-ATPase活性的影响。IGF-I以剂量和时间依赖性方式增加泵活性：所需的最小剂量为10(-10) M，所需的最短时间为20分钟（在10(-8) M时）以增加活性。类似的作用持续12小时。在钠负荷细胞中，IGF-I不会进一步刺激活性。钠/氢交换的阻断在30分钟后减弱IGF-I诱导的活性增加，但在12小时后没有作用。Northern印迹分析显示，泵的α1和α2亚基的表达不受IGF-I的影响。质膜α1和α2蛋白也不受影响，表明预先形成的池的易位不是活性增加的原因。抑制剂显示，酪氨酸激酶活性、RNA转录、蛋白质合成、一氧化氮合酶活性或蛋白激酶C活性均未介导这种IGF-I效应。因此，IGF-I在短期内通过钠/氢交换依赖性但转录/易位非依赖性机制调节钠泵活性。这些数据表明，已知由血管平滑肌细胞产生的IGF-I可能调节高血压和糖尿病等疾病状态下异常的血管张力和生长反应。
