Khan F, Cohen R A, Ruderman N B, Chipkin S R, Coffman J D
Robert Dawson Evans Memorial Department of Clinical Research, Boston University Medical Center, MA, USA.
Vasc Med. 1996;1(3):187-93. doi: 10.1177/1358863X9600100303.
The integrity of endothelium-dependent vasodilation in the skin of patients with insulin-dependent diabetes mellitus (IDDM) is unclear, especially with respect to the role of nitric oxide. To examine this, forearm skin blood flow by laser Doppler flowmetry and total blood flow by venous occlusion plethysmography was measured in response to brachial artery infusions of an endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilator. Peak hyperemic forearm blood flow, following 5 min of arterial occlusion, was also determined. Responses were compared in 11 control subjects and 16 patients with insulin-dependent diabetes mellitus. In ten normal subjects, co-infusion of NG-monomethyl-L-arginine with methacholine produced a significant reduction in total forearm blood flow response to methacholine (p < 0.002), measured by venous occlusion plethysmography, as well as vascular conductance (p < 0.001), confirming that nitric oxide contributes to this response. In contrast, NG-monomethyl-L-arginine had no significant effect on the methacholine-induced increase in forearm skin blood flow measured by laser Doppler flowmetry indicating that factors other than nitric oxide may be involved. Increases in forearm skin blood flow in response to methacholine, sodium nitroprusside and to an ischemic stimulus were not significantly different between the normal subjects and patients with IDDM. Dose-related increases in total forearm blood flow and vascular conductance were not significantly different between control subjects and diabetic patients during infusions of methacholine. The increases in these parameters during infusions of sodium nitroprusside, however, were significantly less in the diabetic group than in the control group (p < 0.05) as was the peak reactive hyperemic blood flow (p < 0.05). Since skin blood flow was not affected, the reduced vasodilator responses to sodium nitroprusside and an ischemic stimulus in the diabetic group are in forearm skeletal muscle. The reduced muscle blood flow does not reflect a decreased vasodilatory capacity, but rather a functional impairment in response to nitric oxide and ischemia since the methacholine dilation was normal. The normal vasodilator responses in the forearm skin, which is predominantly capillary as opposed to arteriovenous anastomatic blood flow, indicate that the response to nitric oxide and an ischemic stimulus in this vascular bed is intact in patients with IDDM. This is, therefore, an unlikely cause of diabetic skin, complications in these areas.
胰岛素依赖型糖尿病（IDDM）患者皮肤中内皮依赖性血管舒张的完整性尚不清楚，尤其是一氧化氮的作用。为了对此进行研究，通过激光多普勒血流仪测量前臂皮肤血流量，并通过静脉阻塞体积描记法测量总血流量，以响应肱动脉输注内皮依赖性（乙酰甲胆碱）和非依赖性（硝普钠）血管舒张剂。还测定了动脉阻塞5分钟后的前臂充血峰值血流量。对11名对照受试者和16名胰岛素依赖型糖尿病患者的反应进行了比较。在10名正常受试者中，将NG-单甲基-L-精氨酸与乙酰甲胆碱共同输注后，通过静脉阻塞体积描记法测量的对乙酰甲胆碱的总前臂血流量反应（p < 0.002）以及血管传导率（p < 0.001）均显著降低，证实一氧化氮促成了这一反应。相比之下，NG-单甲基-L-精氨酸对通过激光多普勒血流仪测量的乙酰甲胆碱诱导的前臂皮肤血流量增加没有显著影响，这表明可能涉及一氧化氮以外的因素。正常受试者和IDDM患者对乙酰甲胆碱、硝普钠和缺血刺激的前臂皮肤血流量增加没有显著差异。在输注乙酰甲胆碱期间，对照受试者和糖尿病患者的总前臂血流量和血管传导率的剂量相关增加没有显著差异。然而，在输注硝普钠期间，糖尿病组这些参数的增加明显低于对照组（p < 0.05），峰值反应性充血血流量也是如此（p < 0.05）。由于皮肤血流量未受影响，糖尿病组对硝普钠和缺血刺激的血管舒张反应降低发生在前臂骨骼肌。肌肉血流量减少并不反映血管舒张能力下降，而是反映对一氧化氮和缺血反应的功能受损，因为乙酰甲胆碱舒张正常。前臂皮肤的正常血管舒张反应主要是毛细血管而非动静脉吻合血流，这表明IDDM患者该血管床对一氧化氮和缺血刺激的反应是完整的。因此，这不太可能是糖尿病皮肤这些区域并发症的原因。
