INSULIN AND ENDOTHELIN ACTIVITY IN THE HUMAN MICROCIRCULATION

探讨高胰岛素血症与胰岛素抵抗的潜在机制。 高血压和动脉粥样硬化，我们研究了胰岛素是否调节 内皮素（ET-1），一种血管收缩剂， 促分裂肽为此，我们测量了前臂血流量 (FBF应变容积描记术）对ET-1受体阻断的反应 在输注生理盐水或胰岛素期间，8名健康受试者在2 分开的日子。在生理盐水、ET/A受体动脉内输注期间 阻断剂（BQ-123，100 nmol/min，60 min），单独使用和与 ET/B受体拮抗剂（BQ-788; 50 nmol/min持续60 min） 未显著改变FBF（之前为2.9 +/-0.2 [平均值+/-SEM] mL/min/dL， BQ-123单独给药后为2.9 +/-0.2 mL/min/dL， BQ-123和BQ-788组合; P = 0.29）。 胰岛素给药（0.1 mU/kg/min，持续2小时）导致局部胰岛素水平显著升高 浓度（从3 +/-1至295 +/-69 microU/mL; P = 0.004），但没有 修改FBF（2.30.1 2小时前为2.2 +/-0.1 mL/min/dL，2小时后为2.2 ± 0.1 mL/min/dL 胰岛素输注组; P = 0.58）。高胰岛素血症时，ET-1受体 拮抗作用引起血管扩张效应，FBF增加25 +/-9% 选择性ET/A阻断60分钟后， 联合ET/A和ET/B拮抗作用（P <0.001）。这些发现表明 胰岛素刺激血管产生ET-1，这可能有助于 高胰岛素血症的高血压和致动脉粥样硬化作用。的 观察到胰岛素不改变血管张力， ET-1受体阻断剂与同时激活 血管扩张机制的生理平衡， ET-1增加的血管收缩作用。

To investigate a potential mechanism linking hyperinsulinemia with hypertension and atherosclerosis, we examined whether insulin modulates the vasoactive effects of endothelin (ET-1), a vasoconstrictor and mitogenic peptide. To this purpose, we measured the forearm blood flow (FBF; strain-gauge plethysmography) responses to ET-1 receptor blockade during infusion of either saline or insulin in 8 healthy subjects on 2 separate days. During saline, intraarterial infusion of an ET/A-receptor blocker (BQ-123, 100 nmol/min for 60 min), alone and in combination with an ET/B-receptor antagonist (BQ-788; 50 nmol/min for further 60 min) did not significantly change FBF (2.9+/-0.2 [mean+/-SEM] mL/min/dL before, 2.9+/-0.2 mL/min/dL after BQ-123 alone, 2.8+/-0.2 mL/min/dL after the combination of BQ-123 and BQ-788; P=0.29). Insulin administration (0.1 mU/kg/min for 2 hr) resulted in a marked increase in local insulin concentration (from 3+/-1 to 295+/-69 microU/mL; P=0.004), but did not modify FBF (2.30.1 mL/min/dL before and 2.2+/-0.1 mL/min/dL after 2 hr of insulin infusion; P=0.58). During hyperinsulinemia, ET-1 receptor antagonism caused a vasodilator effect, with a FBF increase of 25+/-9% after 60 min of selective ET/A blockade and of 52+/-7% after 60 min of combined ET/A and ET/B antagonism (P<0.001). These findings suggest that insulin stimulates vascular production of ET-1, which may contribute to the hypertensive and atherogenic effects of hyperinsulinemia. The observation that insulin does not modify vascular tone in the absence of ET-1 receptor blockade is compatible with the concurrent activation of vasodilator mechanisms that physiologically balance the vasoconstrictor effect of increased ET-1.