Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation
Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation
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DOI：
10.1152/ajpheart.00446.2017
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发表时间：
2018-02-01
影响因子：
4.8
通讯作者：
Alexander, Lacy M.
中科院分区：
文献类型：
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作者：
Alba, Billie K.;Greaney, Jody L.;Alexander, Lacy M.
银屑病是心血管疾病的一个独立危险因素;然而，其潜在机制尚不完全清楚。银屑病患者的导管动脉功能缺陷是明显的，但微循环内皮功能的潜在损害仍不清楚。我们假设皮肤微血管功能障碍在其他健康的银屑病患者中是可以检测到的。将两个皮内微透析纤维放置在（非病变）9例患者的前臂皮肤（3名男性和6名女性，39 +/- 5岁），中度（16 +/- 2%的体表面积）斑块型银屑病和9个健康（非银屑病）对照受试者（3名男性和6名女性，38 ± 5岁），用于局部递送1）乳酸林格氏溶液（对照）和2）10 mM L-抗坏血酸盐（一种非特异性抗氧化剂）。在局部加热（42 ℃）期间使用激光多普勒血流仪测量皮肤血流指数。灌注非特异性NO合酶抑制剂NG-硝基-L-精氨酸甲酯（15 mM）后，直接定量一氧化氮（NO）依赖性血管舒张。第三根纤维灌注递增浓度（10（-10）-10（-2）M）的去甲肾上腺素，以引起肾上腺素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（对照组和银屑病成人患者的最大皮肤血管传导率分别为57 ± 5%和39 ± 7%，P < 0.01）。L-抗坏血酸对NO依赖性血管舒张功能无明显改善作用（P > 0.05）。去甲肾上腺素组间最大血管收缩反应和微血管敏感性差异无统计学意义（P > 0.05）。这些数据表明，NO的生物利用度降低，否则健康的个体与银屑病，这有助于全身微血管dysfunctions.NEW &值得注意的是，在成年银屑病患者中，降低一氧化氮的生物利用度介导受损的内皮依赖性血管舒张，独立于氧化应激的增加。此外，银屑病血管病变的程度与一氧化氮依赖性血管舒张的更大减少直接相关。
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 degrees C). Nitric oxide (NO)-dependent vasodilation was directly quantified after perfusion of the nonspecific NO synthase inhibitor NG-nitro-L-arginine methyl ester (15 mM). A third fiber was perfused with increasing concentrations (10(-10) - 10(-2) 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.