Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation

Abstract

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.

Changes in Microvascular Reactivity and Systemic Vascular Resistance in Patients With Psoriasis

“…This is in agreement with findings of other studies that have demonstrated an elevated cutaneous blood flow in psoriatic plaques compared with nonplaque skin [7]. However, we did not find differences between the cutaneous blood flow in the clinically normal skin of the psoriatic subjects and that of normal subject [8,9]. The increased blood flow can be related to the expanded capillary bed [10] and an increase in the capillary mass as shown by the previous studies [11].…”

“…Studies have shown that NO-mediated endothelium -dependent vasodilation was blunted in patients with psoriasis, and the degree of psoriatic symptomology was significantly related to reduction in NOdependent vasodilation in psoriasis patients suggesting greater disease severity is associated with larger reduction in NO bioavailability [8,9,14]. Contrary to our initial hypothesis, the postocclusive reactive hyperaemia test (PORH) did not reveal any significant differences between the LDF in plaques and non-plaque skin.…”

Historical reviews of the assessment of human cardiovascular function: interrogation and understanding of the control of skin blood flow

“…The intradermal microdialysis technique was originally developed to sample neurotransmitters in neural tissue in rodent models (Ungerstedt and Hallstrom 1987). The technique has several applications ranging from the recovery of tissue metabolites (Petersen et al 1992;Alba et al 2018), delivery of pharmacological agents (Alexander et al 2013;Craighead et al 2017;Smith et al 2013Smith et al , 2017, and estimation of localised blood flow in tissues (Hickner et al 1992). Laser Doppler flux is the main outcome measure in studies utilising intradermal microdialysis (see Fig.…”

Delivering nitric oxide into human skin from encapsulated S-nitrosoglutathione under UV light: An in vitro and ex vivo study

“…UV irradiation, at specific wavelengths, allied to the topical application of GSNO-CS NPs further increased RSNO levels in human skin, as reported in this work. This increase of NO and RSNO levels in human skin might have positive effects on the cardiovascular system, as previously discussed[6][7][8]10,30,54,55].…”