Mäkimattila S, Mäntysaari M, Groop P H, Summanen P, Virkamäki A, Schlenzka A, Fagerudd J, Yki-Järvinen H
Department of Medicine, Helsinki (Finland) University Central Hospital, Finland.
Circulation. 1997 Feb 4;95(3):618-25. doi: 10.1161/01.cir.95.3.618.
The link between diabetes and vascular disease is poorly understood. Data regarding endothelial function in vivo in patients with insulin-dependent diabetes mellitus (IDDM) have been inconsistent with in vitro studies demonstrating hyperglycemia-induced impairments in endothelium-dependent vasodilation.
We determined whether alterations in neural control of the vascular tone might contribute to blood flow responses to intrabrachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and L-N-monomethyl-arginine (L-NMMA) in 22 men with IDDM (12 with normoalbuminuria. HbA1c = 8.6 +/- 0.3%; 10 with macroalbuminuria, HbA1c = 8.6 +/- 0.3%) and 11 matched normal men. Autonomic function was assessed from reflex vasoconstriction to cold, the blood pressure response to standing and hand grip, and heart rate variation, including spectral analysis, during controlled breathing, and the Valsalva maneuver. IDDM with macroalbuminuria exhibited hyperresponsiveness to both ACh and SNP compared with the patients with normoalbuminuria or normal subjects. Reflex sympathetic vasoconstriction to cold was severely impaired in the IDDM patients with macroalbuminuria (-19 +/- 6%) compared with normoalbuminuric patients (-39 +/- 5%, P < .05) and normal subjects (-54 +/- 7%, P < .001). The macroalbuminuric patients also had evidence of autonomic dysfunction during controlled and deep breathing tests and during the Valsalva maneuver. Within the group of IDDM patients, neither the urinary albumin excretion rate nor other parameters such as HbA1c or serum cholesterol correlated with forearm blood flow during the vasoactive drug infusions. There were, however, significant inverse correlations between several measures of both sympathetic and parasympathetic autonomic functions and vascular hyperresponsiveness to SNP and ACh. For example, the Valsalva ratio was inversely correlated with the increase in blood flow in response to infusion of 3 (r = -.74, P < .001) and 10 (r = -.73, P < .001) micrograms/min SNP and 7.5 (r = -.73, P < .001) and 15 (r = -.75, P < .001) micrograms/min ACh.
These data are consistent with idea that altered neurotransmission is an important determinant of vascular reactivity of diabetic blood vessels to nitrovasodilators in vivo.
糖尿病与血管疾病之间的联系尚不清楚。关于胰岛素依赖型糖尿病（IDDM）患者体内内皮功能的数据与体外研究结果不一致，体外研究表明高血糖会导致内皮依赖性血管舒张功能受损。
我们测定了22例IDDM男性患者（12例正常白蛋白尿，糖化血红蛋白[HbA1c]=8.6±0.3%；10例大量白蛋白尿，HbA1c=8.6±0.3%）和11例匹配的正常男性对肱动脉内输注乙酰胆碱（ACh）、硝普钠（SNP）和L-N-单甲基精氨酸（L-NMMA）时血流反应中血管张力神经控制的改变情况。通过对冷刺激的反射性血管收缩、站立和握力时的血压反应以及包括频谱分析在内的心率变化来评估自主神经功能，这些评估在控制呼吸和瓦尔萨尔瓦动作期间进行。与正常白蛋白尿患者或正常受试者相比，大量白蛋白尿的IDDM患者对ACh和SNP均表现出高反应性。与正常白蛋白尿患者（-39±5%，P<.05）和正常受试者（-54±7%，P<.001）相比，大量白蛋白尿的IDDM患者对冷刺激的反射性交感神经血管收缩严重受损（-19±6%）。大量白蛋白尿患者在控制呼吸和深呼吸试验以及瓦尔萨尔瓦动作期间也有自主神经功能障碍的证据。在IDDM患者组中，血管活性药物输注期间尿白蛋白排泄率以及其他参数如HbA1c或血清胆固醇与前臂血流均无相关性。然而，交感神经和副交感神经自主神经功能的多项测量指标与对SNP和ACh的血管高反应性之间存在显著负相关。例如，瓦尔萨尔瓦比值与输注3（r=-.74，P<.001）和10（r=-.73，P<.001）微克/分钟SNP以及7.5（r=-.73，P<.001）和15（r=-.75，P<.001）微克/分钟ACh时血流增加呈负相关。
这些数据与以下观点一致，即神经传递改变是糖尿病血管在体内对硝基血管扩张剂血管反应性的重要决定因素。
