INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION IS NITRIC-OXIDE DEPENDENT - A NOVEL ACTION OF INSULIN TO INCREASE NITRIC-OXIDE RELEASE
INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION IS NITRIC-OXIDE DEPENDENT - A NOVEL ACTION OF INSULIN TO INCREASE NITRIC-OXIDE RELEASE
复制标题
DOI：
10.1172/jci117433
复制
发表时间：
1994-09-01
影响因子：
15.9
通讯作者：
BARON, AD
中科院分区：
文献类型：
--
作者：
STEINBERG, HO;BRECHTEL, G;BARON, AD
本研究的目的是研究胰岛素对血管扩张骨骼肌血管的作用是否通过内皮源性一氧化氮（EDNO）介导。将NO合成酶特异性抑制剂N-单甲基-L-精氨酸（L-NMMA）以16 mg/min的剂量直接注入正常受试者的股动脉，并在输注生理盐水（NS）或设计为使下肢血流量（LBF）约加倍的正常血糖高胰岛素钳夹（HIC）期间测量下肢血流量（LBF）。股动脉灌注L-NMMA后，NS期间LBF从0.296+/-0.032降到0.235+/-0.022升/分，HIC期间LBF从0.479+/-0.118降到0.266+/-0.052升/分，P < 0.03。NS和HIC时NO依赖性LBF的比例分别为20%和40%，P < 0.003（NS vs. HIC）。为了阐明胰岛素是否增加EDNO的合成/释放或EDNO的作用，在NS或HIC期间研究了正常受试者对内皮依赖性血管扩张剂乙酰甲胆碱氯化物（MCh）或内皮非依赖性血管扩张剂硝普钠（SNP）的分级股动脉输注的血管扩张反应。股动脉灌注MCh后LBF增加，HIC组与NS组相比，差异有统计学意义（P < 0.03）。总之，胰岛素介导的血管舒张是EDNO依赖性的。骨骼肌血管系统的胰岛素血管舒张最可能通过增加EDNO合成/释放而发生。因此，胰岛素似乎是EDNO系统的新调节剂。
The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, was administered directly into the femoral artery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF) was measured during an infusion of saline (NS) or during a euglycemic hyperinsulinemic clamp (HIC) designed to approximately double LBF. In response to the intrafemoral artery infusion of L-NMMA, LBF decreased from 0.296+/-0.032 to 0.235+/-0.022 liters/min during NS and from 0.479+/-0.118 to 0.266+/-0.052 liters/min during HIC, P < 0.03. The proportion of NO-dependent LBF during NS and HIC was similar to 20% and similar to 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate whether insulin increases EDNO synthesis/release or EDNO action, vasodilative responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) were studied in normal subjects during either NS or HIC. LBF increments in response to intrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.