Moore J W, Maher M A, Banz W J, Zemel M B
Departments of Nutrition and Medicine, The University of Tennessee, Knoxville, TN 37996-1900, USA.
J Nutr. 1998 Feb;128(2):180-4. doi: 10.1093/jn/128.2.180.
We have previously shown that insulin attenuates vasoconstriction, accelerates both vascular relaxation and [Ca2+]i recovery from pressor agonist-induced Ca2+ loads, and stimulates Ca2+-ATPase gene expression in rat and human vascular smooth muscle cells (VSMC). Moreover, these functions are impaired in VSMC from both insulin resistant and insulinopenic rats, suggesting that hypertension in insulin resistant states may result, in part, from impaired insulin-regulation of VSMC Ca2+ transport. Accordingly, we have now evaluated the effect of improving cellular insulin sensitivity with chromium picolinate (CrPic) on regulation of VSMC Ca2+ transport. Cultured VSMC from rats were grown from passage to confluence in the presence or absence of 1 micromol/L CrPic, maintained in a quiescent medium for 24 h and incubated with or without insulin (10(-8) mol/L) for the final 2 h. Cells were then harvested and RNA and protein extracted for Northern and Western blot analysis, respectively. Insulin caused a significant stimulation of plasmalemmal Ca2+-ATPase mRNA and protein (P < 0.05). A comparable stimulation of the mRNA and protein levels was caused by CrPic in the absence of insulin (P < 0.05), while the CrPic + insulin treatment caused a greater percentage stimulation of the Ca2+-ATPase mRNA level than either separate treatment (P < 0.05). Fluorometric analysis of the rate of [Ca2+]i recovery following stimulation with arginine vasopressin support these findings: insulin caused an 83% increase, CrPic caused a 35% increase and insulin + CrPic caused a 133% increase in [Ca2+]i recovery rate. These data suggest that CrPic may be an effective modality to reduce VSMC [Ca2+]i loads and thereby reduce peripheral vascular resistance in insulin resistant states.
我们之前已经表明，胰岛素可减弱血管收缩，加速血管舒张以及从升压激动剂诱导的钙负荷中恢复细胞内钙离子浓度（[Ca2+]i），并刺激大鼠和人血管平滑肌细胞（VSMC）中Ca2+-ATP酶基因的表达。此外，胰岛素抵抗和胰岛素缺乏大鼠的VSMC中这些功能受损，这表明胰岛素抵抗状态下的高血压可能部分源于VSMC钙转运的胰岛素调节受损。因此，我们现在评估了用吡啶甲酸铬（CrPic）改善细胞胰岛素敏感性对VSMC钙转运调节的影响。将来自大鼠的培养VSMC在存在或不存在1微摩尔/升CrPic的情况下从传代培养至汇合，在静态培养基中维持24小时，并在最后2小时与或不与胰岛素（10^(-8)摩尔/升）一起孵育。然后收获细胞并分别提取RNA和蛋白质用于Northern和Western印迹分析。胰岛素显著刺激了质膜Ca2+-ATP酶的mRNA和蛋白质表达（P < 0.05）。在没有胰岛素的情况下，CrPic对mRNA和蛋白质水平产生了类似的刺激作用（P < 0.05），而CrPic +胰岛素处理对Ca2+-ATP酶mRNA水平的刺激百分比高于单独处理（P < 0.05）。用精氨酸加压素刺激后对[Ca2+]i恢复速率的荧光分析支持了这些发现：胰岛素使[Ca2+]i恢复速率增加83%，CrPic使[Ca2+]i恢复速率增加35%，胰岛素 + CrPic使[Ca2+]i恢复速率增加133%。这些数据表明，CrPic可能是一种有效的方法，可减少VSMC中的[Ca2+]i负荷，从而降低胰岛素抵抗状态下的外周血管阻力。
