Lembo G, Iaccarino G, Vecchione C, Barbato E, Izzo R, Fontana D, Trimarco B
IRCCS "INM NEUROMED," Pozzilli (IS), Italy.
J Clin Invest. 1997 Oct 15;100(8):2007-14. doi: 10.1172/JCI119732.
We explored in 51 normal subjects, distributed in various series of experiments, whether endothelium nitric oxide may play a role in insulin modulation of alpha2- and beta-adrenergic- evoked vascular responses. In particular, we examined the forearm blood flow response (FBF, ml.min-1.dl-1) to intrabrachial infusion of BHT-933 (0.5, 1, and 2 microg.min-1.dl-1) or isoproterenol (1, 3, and 6 ng. min-1.dl-1) in control conditions, during intrabrachial infusion of insulin alone (0.05 mU.kg-1.min-1) and associated with l-N-monomethylarginine (L-NMMA) (0.05 microg.min-1.dl-1), a nitric oxide synthase inhibitor. In control conditions both BHT-933 and isoproterenol induced a dose-dependent vascular response. Local hyperinsulinemia (deep venous plasma insulin 68.5+/-4 microU/ml) did not change basal FBF whereas attenuated BHT-933 vasoconstriction and enhanced isoproterenol vasodilation. L-NMMA reduced basal FBF and abolished the insulin effect on BHT-933 and isoproterenol response. To clarify whether a nitric oxide component is included in alpha2- and beta-adrenergic response and may be responsible for insulin vascular effect, we further examined BHT-933 and isoproterenol responses during nitric oxide inhibition. Interestingly, L-NMMA potentiated the BHT-933 vasoconstriction and attenuated the isoproterenol vasodilation and, in these conditions, insulin was no more able to exhibit its vascular effects. Finally, to rule out the possibility that the conteracting effect of L-NMMA may not be specifically related to insulin action, dose-response curves to phenylephrine (0.5, 1, and 2 microg.min-1.dl-1) or sodium nitroprusside (1, 2, and 4 microg.min-1.dl-1) were also performed. Both insulin and L-NMMA were unable to alter the phenylephrine-induced vasoconstriction and the sodium nitroprusside vasodilation. In conclusion, our data demonstrate an endothelial nitric oxide component in the alpha2- and beta-adrenergic vascular responses which is the target of the insulin vascular action.
我们在51名正常受试者中进行了多项系列实验，探究内皮一氧化氮是否在胰岛素对α2和β肾上腺素能诱发的血管反应的调节中发挥作用。具体而言，我们检测了在对照条件下、单独进行肱动脉内输注胰岛素（0.05 mU·kg-1·min-1）以及与一氧化氮合酶抑制剂L-N-单甲基精氨酸（L-NMMA，0.05 μg·min-1·dl-1）联合使用时，肱动脉内输注BHT-933（0.5、1和2 μg·min-1·dl-1）或异丙肾上腺素（1、3和6 ng·min-1·dl-1）后前臂血流量反应（FBF，ml·min-1·dl-1）。在对照条件下，BHT-933和异丙肾上腺素均诱导出剂量依赖性血管反应。局部高胰岛素血症（深静脉血浆胰岛素68.5±4 μU/ml）未改变基础FBF，但减弱了BHT-933的血管收缩作用并增强了异丙肾上腺素的血管舒张作用。L-NMMA降低了基础FBF，并消除了胰岛素对BHT-933和异丙肾上腺素反应的影响。为了阐明一氧化氮成分是否包含在α2和β肾上腺素能反应中并可能是胰岛素血管作用的靶点，我们在一氧化氮抑制期间进一步检测了BHT-933和异丙肾上腺素的反应。有趣的是，L-NMMA增强了BHT-933的血管收缩作用并减弱了异丙肾上腺素的血管舒张作用，在这些条件下，胰岛素不再能够发挥其血管效应。最后，为了排除L-NMMA的拮抗作用可能与胰岛素作用无特异性关联的可能性，我们还进行了去氧肾上腺素（0.5、1和2 μg·min-1·dl-1）或硝普钠（1、2和4 μg·min-1·dl-1）的剂量反应曲线实验。胰岛素和L-NMMA均无法改变去氧肾上腺素诱导的血管收缩作用以及硝普钠的血管舒张作用。总之，我们的数据表明，α2和β肾上腺素能血管反应中存在内皮一氧化氮成分，它是胰岛素血管作用的靶点。
