INSULIN AND ENDOTHELIN ACTIVITY IN THE HUMAN MICROCIRCULATION

探讨高胰岛素血症与糖尿病的潜在机制 高血压和动脉粥样硬化，我们检查了胰岛素是否调节 血管紧张剂内皮素(ET-1)的血管活性作用 有丝分裂多肽。为此，我们测量了前臂的血流量 (FBF；应变计体积描记术)对ET-1受体阻断的反应 在给8名健康受试者输注生理盐水或胰岛素期间 分开的几天。在生理盐水期间，动脉内输注ET/A受体 阻滞剂(BQ-123,100nmol/分钟，作用60分钟)，单独或与 ET/B受体拮抗剂(BQ-788；50nmol/min，再作用60min)起作用 治疗前FBF(2.9+/-0.2[Mean+/-Sm]m L/min/dL)无明显变化， 单独使用BQ-123后2.9+/-0.2毫升/分钟/分升，使用BQ-123后2.8+/-0.2毫升/分/分 BQ-123和BQ-788联合使用；P=0.29)。胰岛素注射(0.1 MU/kg/min持续2小时)导致局部胰岛素显著增加 浓度(从3+/-1到295+/-69微U/毫升；P=0.004)，但没有 修改FBF(前2.30.1毫升/分/分升，2小时后2.2+/-0.1毫升/分/分升 胰岛素输注率；P=0.58)。高胰岛素血症时ET-1受体 拮抗引起血管扩张效应，FBF增加25+/-9% 选择性ET/A阻断60min后52%+/-7% ET/A和ET/B联合拮抗作用(P&lt；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 高胰岛素血症对高血压和动脉粥样硬化的影响。这个 观察胰岛素在缺乏时不改变血管张力 ET-1受体阻断与同时激活相容 血管扩张剂的生理平衡机制 ET-1升高的血管收缩作用。

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.