Tack C J, Heeremans M, Thien T, Lutterman J A, Smits P
Department of Medicine, University Hospital Nijmegen, The Netherlands.
J Cardiovasc Pharmacol. 1996 Aug;28(2):245-51. doi: 10.1097/00005344-199608000-00010.
The relation between insulin resistance/ hyperinsulinemia and cardiovascular disease may be related to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is activated, although this does not lead to increase in blood pressure (BP). We hypothesized that insulin could induce vasodilation either by reduction of alpha- or by augmentation of beta-adrenergic responsiveness. The effect of insulin infusion into the brachial artery (regional forearm hyperinsulinemia; venous insulin concentration approximately 500 pM) on forearm blood flow (FBF: plethysmography) was studied. Responses to the alpha-adrenoceptor-mediated vasoconstrictor norepinephrine (NE: once with and once without the beta-adrenoceptor antagonist propranolol, 2 x n = 12; 9 participated in both), and to the beta-adrenoceptor-mediated vasodilator isoproterenol (n = 12) were measured before and during local hyperinsulinemia. Time/control studies (n = 6) were performed. Insulin alone induced vasodilation, as indicated by an increase in FBF-ratio (infused/ control arm) from 1.2 +/- 0.1 to 1.6 +/- 0.2, p = 0.009. Increasing dosages of NE (1.25 to 240 ng.dl-1.ml-1) induced vasoconstriction that was more pronounced during concomitant propranolol infusion (p < 0.001), indicating a dose-dependent vasodilatory component in the effect of NE. Isoproterenol (ISO 0.03 to 10 ng.dl-1.ml-1), a pure beta-adrenoceptor agonist, induced vasodilation. The percentage changes of FBF-ratio during NE+propranolol were similar and not significantly different before and during hyperinsulinemia. The same was true of the response to NE alone and the response to ISO. Neither was the intrinsic beta-agonist component of NE influenced by insulin. Repeated NE infusion showed no time- or vehicle effect. We conclude that regional hyperinsulinemia in the physiological range induces local vasodilation in the skeletal muscle vascular bed, but this vasodilation is not mediated through modulation of alpha- or beta-adrenergic responsiveness.
胰岛素抵抗/高胰岛素血症与心血管疾病之间的关系可能与胰岛素的一种心血管效应有关。在人体急性实验中，全身性正常血糖高胰岛素血症可诱导骨骼肌血管舒张。此外，交感神经系统被激活，尽管这不会导致血压升高。我们推测胰岛素可通过降低α-肾上腺素能反应性或增强β-肾上腺素能反应性来诱导血管舒张。研究了向肱动脉输注胰岛素（局部前臂高胰岛素血症；静脉胰岛素浓度约500 pM）对前臂血流量（FBF：体积描记法）的影响。在局部高胰岛素血症之前和期间，测量对α-肾上腺素能受体介导的血管收缩剂去甲肾上腺素（NE：一次加β-肾上腺素能受体拮抗剂普萘洛尔，一次不加，2×n = 12；9人参与了两次）以及对β-肾上腺素能受体介导的血管舒张剂异丙肾上腺素（n = 12）的反应。进行了时间/对照研究（n = 6）。单独胰岛素可诱导血管舒张，如FBF比率（输注/对照臂）从1.2±±0.1增加到1.6±±0.2所示，p = 0.009。增加剂量的NE（1.25至240 ng.dl-1.ml-1）可诱导血管收缩，在同时输注普萘洛尔时更明显（p < 0.001），表明NE作用中存在剂量依赖性血管舒张成分。异丙肾上腺素（ISO 0.03至10 ng.dl-1.ml-1），一种纯β-肾上腺素能受体激动剂，可诱导血管舒张。在NE +普萘洛尔期间FBF比率的百分比变化在高胰岛素血症之前和期间相似且无显著差异。单独对NE的反应和对ISO的反应也是如此。NE的内在β-激动剂成分也不受胰岛素影响。重复输注NE未显示时间或载体效应。我们得出结论，生理范围内的局部高胰岛素血症可诱导骨骼肌血管床局部血管舒张，但这种血管舒张不是通过调节α-或β-肾上腺素能反应性介导的。
