Vervoort G, Wetzels J F, Lutterman J A, van Doorn L G, Berden J H, Smits P
Department of General Internal Medicine, University Hospital Nijmegen St Radboud, Nijmegen, The Netherlands.
Hypertension. 1999 Nov;34(5):1080-5. doi: 10.1161/01.hyp.34.5.1080.
Capillary hyperperfusion precedes and contributes to the occurrence of diabetic microangiopathy. Vascular tone is regulated by the balance of vasodilating and vasoconstricting factors, of which nitric oxide (NO; an endothelium dependent vasodilator) and norepinephrine (NE; a potent vasoconstrictor), respectively, are of primary importance. To investigate the role of these factors in hyperperfusion, we measured forearm blood flow (FBF) in 50 patients with noncomplicated type 1 diabetes (DP) and 50 healthy control subjects (CS) under baseline conditions and during intrabrachial infusion of N(G)-monomethyl-L-arginine (L-NMMA), an endothelium-dependent vasoconstrictor, and acetylcholine (ACh), an endothelium-dependent vasodilator. Furthermore, we determined arterial plasma NE concentration at baseline and then determined alpha-adrenergic receptor sensitivity by measuring FBF response to intra-arterially infused NE. We found that basal FBF was increased in DP (2.9+/-0.1 versus 2.0+/-0.1 mL. min(-1). dL(-1) in CS; P<0.01). L-NMMA caused a similar vasoconstriction in both groups (28.5+/-1. 7% in DP versus 31.2+/-2.2% in CS; P=NS). Maximum blood flow during infusion of ACh was not different (23.3+/-1.9 mL. min(-1). dL(-1) in DP versus 20.1+/-1.6 in CS). Arterial plasma NE concentrations were significantly decreased in DP (0.57+/-0.03 versus 0.81+/-0.05 nmol/L in CS; P<0.01). The vasoconstrictive effect of NE was increased in DP (slope log dose-response curve, 31.3+/-1.5 versus 24.3+/-1.8 in CS; P<0.01). We conclude that basal FBF is increased in noncomplicated type 1 diabetes. We found no evidence of a disturbance of basal or stimulated NO production. Arterial plasma NE concentrations are decreased in noncomplicated type 1 diabetes. This may explain the vasodilatation at baseline and the increased vascular response to intra-arterially NE.
毛细血管高灌注先于糖尿病微血管病变并促使其发生。血管张力由血管舒张因子和血管收缩因子的平衡调节，其中一氧化氮（NO；一种内皮依赖性血管舒张剂）和去甲肾上腺素（NE；一种强效血管收缩剂）分别起主要作用。为研究这些因素在高灌注中的作用，我们在基线条件下以及在肱动脉内输注内皮依赖性血管收缩剂N(G)-单甲基-L-精氨酸（L-NMMA）和内皮依赖性血管舒张剂乙酰胆碱（ACh）期间，测量了50例非复杂性1型糖尿病患者（DP）和50例健康对照者（CS）的前臂血流量（FBF）。此外，我们在基线时测定动脉血浆NE浓度，然后通过测量对动脉内输注NE的FBF反应来确定α-肾上腺素能受体敏感性。我们发现DP组的基础FBF增加（DP组为2.9±0.1，而CS组为2.0±0.1 mL·min⁻¹·dL⁻¹；P<0.01）。L-NMMA在两组中引起相似的血管收缩（DP组为28.5±1.7%，CS组为31.2±2.2%；P=无显著差异）。输注ACh期间的最大血流量无差异（DP组为23.3±1.9 mL·min⁻¹·dL⁻¹，CS组为20.1±1.6）。DP组动脉血浆NE浓度显著降低（DP组为0.57±0.03，CS组为0.81±0.05 nmol/L；P<0.01）。DP组中NE的血管收缩作用增强（斜率对数剂量反应曲线，DP组为31.3±1.5，CS组为24.3±1.8；P<0.01）。我们得出结论，非复杂性1型糖尿病患者的基础FBF增加。我们没有发现基础或刺激的NO产生受到干扰的证据。非复杂性1型糖尿病患者动脉血浆NE浓度降低。这可能解释了基线时的血管舒张以及对动脉内NE的血管反应增加。
