Hodges Gary J, Nawaz Shah, Tew Garry A
Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
Sheffield Vascular Institute, Northern General Hospital, Sheffield, UK.
Clin Hemorheol Microcirc. 2015;59(1):83-95. doi: 10.3233/CH-141838.
Peripheral arterial disease (PAD) is associated with cutaneous microvascular dysfunction and an increased risk of arterial ulceration in the affected lower-limb(s). The purpose of this study was to investigate the role of nitric oxide (NO) in cutaneous microvascular dysfunction in patients with PAD. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in 5 patients with unilateral symptomatic PAD and 10 age-matched healthy controls at baseline and during 40 min of local skin heating to 42°C at 1) untreated lower-leg sites, and 2) lower-leg sites treated with 20 mM N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase activity. SkBF was expressed as laser-Doppler flux (LDF) and normalized to maximal LDF (%LDF(max)) achieved through localized heating to 44°C and concomitant infusion of 56 mM sodium nitroprusside. Pharmacological agents and control treatments (lactated Ringer's) were administered using intradermal microdialysis. The plateau LDF response to local skin warming at the untreated skin sites was significantly (P<0.05) lower in the diseased limb of the PAD patients (70.3±13.6 %max) compared to the non-diseased contralateral limb (85.0±10.2 %max) and the response observed for the control participants (89.0±5.2 %max). The NO contribution to the plateau SkBF response tended to be lower in the diseased limb of the PAD patients (45.1±16.4% versus 56.1±10.7% [P=0.12] and 55.4±11.5% [P=0.13], respectively). The results suggest that PAD impairs downstream cutaneous microvascular vasodilatory function and that the microvascular dysfunction is probably explained, at least in part, by a reduced NO signal.
外周动脉疾病（PAD）与皮肤微血管功能障碍以及患侧下肢动脉溃疡风险增加相关。本研究旨在探讨一氧化氮（NO）在PAD患者皮肤微血管功能障碍中的作用。我们使用激光多普勒血流仪，在基线时以及在将局部皮肤加热至42°C持续40分钟的过程中，测量了5例单侧有症状PAD患者和10例年龄匹配的健康对照者的皮肤血流量（SkBF），测量部位为：1）未治疗的小腿部位；2）用20 mM N(G)-硝基-L-精氨酸甲酯（L-NAME）处理以抑制NO合酶活性的小腿部位。SkBF以激光多普勒通量（LDF）表示，并通过局部加热至44°C并同时输注56 mM硝普钠将其标准化为最大LDF（%LDF(max)）。使用皮内微透析给予药理剂和对照处理（乳酸林格液）。与对侧未患病肢体（85.0±10.2 %max）和对照参与者观察到的反应（89.0±5.2 %max）相比，PAD患者患病肢体在未治疗皮肤部位对局部皮肤升温的平台期LDF反应显著降低（P<0.05）（70.3±13.6 %max）。NO对平台期SkBF反应的贡献在PAD患者患病肢体中往往较低（分别为45.1±16.4%与56.1±10.7% [P=0.12]和55.4±11.5% [P=0.13]）。结果表明，PAD损害下游皮肤微血管舒张功能，并且微血管功能障碍可能至少部分是由NO信号减少所解释。
