Ouchi Y, Han S Z, Kim S, Akishita M, Kozaki K, Toba K, Orimo H
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Diabetes. 1996 Jul;45 Suppl 3:S55-8. doi: 10.2337/diab.45.3.s55.
To investigate the role of hyperinsulinemia/insulin resistance in vasomotor tone regulation, we studied the effects of vasoactive substances on tension and intracellular free calcium concentration ([Ca2+]i) of aortic smooth muscle derived from rats that were made hyperinsulinemic by insulin infusion and from Zucker obese rats with insulin resistance. The tension and [Ca2+]i of fura 2-loaded aortic strip preparations without endothelium were simultaneously measured by using a fluorimeter. Ten male Wistar rats received a continuous subcutaneous infusion of insulin (18 nmol x kg(-1) x day(-1)) for 2 weeks with osmotic minipumps (INS group). A control group of 10 rats received vehicle. The plasma immunoreactive insulin concentration in the INS group increased to 930 +/- 54 pmol/l. The increase in [Ca2+]i and tension by KCl and phenylephrine (PE) were lower in the INS group without alteration of the [Ca2+]i-tension relationship. The responses to serotonin (5-HT) in the INS group were similar to those in the control group. In contrast, responses to KCl, PE and 5-HT were markedly enhanced in Zucker obese rats compared with those in Zucker lean rats. The pretreatment of aortic preparations from lean rats with Bay K8644 significantly enhanced the responses to KCl to the level observed in the preparations from obese rats; however, Bay K 8644 failed to affect the responses to KCl in obese rats. These results suggest that enhanced vascular contractile responses to vasoactive substances, possibly due to altered function of the voltage-dependent Ca2+ channel in vascular smooth muscle, may play an important role in the pathogenesis of hypertension in the insulin resistance syndrome.
为研究高胰岛素血症/胰岛素抵抗在血管舒缩张力调节中的作用，我们研究了血管活性物质对胰岛素输注诱导的高胰岛素血症大鼠及胰岛素抵抗的Zucker肥胖大鼠主动脉平滑肌张力和细胞内游离钙浓度（[Ca2+]i）的影响。采用荧光计同时测量无内皮的fura 2标记的主动脉条标本的张力和[Ca2+]i。10只雄性Wistar大鼠用渗透微型泵连续皮下输注胰岛素（18 nmol·kg-1·d-1）2周（INS组）。10只大鼠的对照组输注溶媒。INS组血浆免疫反应性胰岛素浓度增至930±54 pmol/l。INS组中氯化钾和去氧肾上腺素（PE）诱导的[Ca2+]i和张力增加较低，而[Ca2+]i-张力关系未改变。INS组对5-羟色胺（5-HT）的反应与对照组相似。相反，与Zucker瘦鼠相比，Zucker肥胖大鼠对氯化钾、PE和5-HT的反应明显增强。用Bay K8644预处理瘦鼠的主动脉标本可显著增强对氯化钾的反应，使其达到肥胖大鼠标本中观察到的水平；然而，Bay K8644未能影响肥胖大鼠对氯化钾的反应。这些结果表明，血管对血管活性物质的收缩反应增强，可能是由于血管平滑肌中电压依赖性Ca2+通道功能改变，这可能在胰岛素抵抗综合征高血压发病机制中起重要作用。
