Department of Kinesiology, The Pennsylvania State University, Noll Laboratory , University Park, Pennsylvania.
Penn State Hershey Medical Group , State College, Pennsylvania.
Am J Physiol Heart Circ Physiol. 2018 Feb 1;314(2):H343-H349. doi: 10.1152/ajpheart.00446.2017. Epub 2017 Oct 20.
Psoriasis is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not fully understood. Deficits in conduit arterial function are evident in patients with psoriasis, but potential impairments in microcirculatory endothelial function remain unclear. We hypothesized that cutaneous microvascular dysfunction would be detectable in otherwise healthy individuals with psoriasis. Two intradermal microdialysis fibers were placed in (nonlesional) forearm skin of nine patients (3 men and 6 women, 39 ± 5 yr) with moderate (16 ± 2% of body surface area) plaque psoriasis and nine healthy (nonpsoriatic) control subjects (3 men and 6 women, 38 ± 5 yr) for local delivery of 1) lactated Ringer solution (control) and 2) 10 mM l-ascorbate (a nonspecific antioxidant). An index of skin blood flow was measured using laser-Doppler flowmetry during local heating (42°C). Nitric oxide (NO)-dependent vasodilation was directly quantified after perfusion of the nonspecific NO synthase inhibitor N-nitro-l-arginine methyl ester (15 mM). A third fiber was perfused with increasing concentrations (10 - 10 M) of norepinephrine to elicit adrenoreceptor-mediated cutaneous vasoconstriction. NO-dependent vasodilation was attenuated in patients with psoriasis (57 ± 5% and 39 ± 7% maximum cutaneous vascular conductance in control subjects and adults with psoriasis, respectively, P < 0.01). l-Ascorbate did not improve NO-dependent vasodilation ( P > 0.05). There was no group difference in maximal vasoconstriction or microvascular sensitivity to norepinephrine ( P > 0.05). These data suggest that NO bioavailability is reduced in otherwise healthy individuals with psoriasis, which contributes to systemic microvascular dysfunction. NEW & NOTEWORTHY In adults with psoriasis, reduced nitric oxide bioavailability mediates impaired endothelium-dependent vasodilation, independent of increases in oxidative stress. Furthermore, the degree of psoriatic symptomology is directly related to greater reductions in nitric oxide-dependent vasodilation.
银屑病是心血管疾病的独立危险因素；然而，其潜在机制尚未完全阐明。银屑病患者的大血管功能明显受损，但微血管内皮功能的潜在损害尚不清楚。我们假设在没有其他疾病的银屑病患者中可以检测到皮肤微血管功能障碍。在 9 名患有中度（16±2%体表面积）斑块型银屑病的患者（3 名男性和 6 名女性，39±5 岁）和 9 名健康对照者（非银屑病患者，3 名男性和 6 名女性，38±5 岁）的前臂非皮损皮肤中，分别放置了 2 个皮内微透析纤维，用于局部输注 1）乳酸林格溶液（对照）和 2）10mM l-抗坏血酸（一种非特异性抗氧化剂）。在局部加热（42°C）时，使用激光多普勒血流仪测量皮肤血流量指数。在输注非特异性一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯（15mM）后，直接定量一氧化氮（NO）依赖性血管舒张。用浓度逐渐增加（10 - 10 M）的去甲肾上腺素灌注第三条纤维以引起肾上腺素能受体介导的皮肤血管收缩。银屑病患者的 NO 依赖性血管舒张减弱（对照和银屑病患者的最大皮肤血管传导分别为 57±5%和 39±7%，P<0.01）。l-抗坏血酸不能改善 NO 依赖性血管舒张（P>0.05）。组间最大血管收缩或去甲肾上腺素对微血管的敏感性无差异（P>0.05）。这些数据表明，NO 生物利用度降低导致健康银屑病患者的全身微血管功能障碍。银屑病患者的 NO 生物利用度降低，导致内皮依赖性血管舒张受损，与氧化应激增加无关。此外，银屑病的症状严重程度与 NO 依赖性血管舒张的降低程度直接相关。
