The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin
Klede, Monika, Clough, Geraldine, Lischetzki, Grischa and Schmelz, Martin (2003) The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin. Journal of Vascular Research, 40, (2), 105-114. (doi:10.1159/000070707).
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Endogenous neuropeptides released from nociceptors can induce vasodilation and enhanced protein extravasation (neurogenic inflammation). The role of nitric oxide (NO) in the induction of neurogenic inflammation is controversial. In this study, dermal microdialysis was used in awake humans (n = 39) to deliver substance P (SP; 10-7 and 10-6M) or calcitonin gene-related peptide (CGRP; 5 × 10-7M and 2 × 10-6M). Neuropeptide-induced local and axon reflex erythema was assessed by laser Doppler imaging. Total protein concentration in the dialysate was measured to quantify local protein extravasation.
The responses were assessed in the absence and the presence of the nitric oxide synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME) added to the perfusate at concentrations of 5, 10 or 20 mM. L-NAME (5 mM) applied via the dialysis catheters reduced local blood flow by approximately 30%. In addition, L-NAME inhibited SP-induced vasodilation by about 40% for 10-7M SP and 30% for 10-6M SP (n = 11, p < 0.01). In contrast, CGRP-induced vasodilation was only marginally inhibited by L-NAME. SP, but not CGRP, provoked a dose-dependent increase in protein extravasation. L-NAME (5 mM) inhibited this increase by up to 40% for both SP concentrations used (n = 11, p < 0.01). Higher concentrations of L-NAME did not further reduce SP- or CGRP-induced vasodilation or SP-induced protein extravasation. Exogenously applied SP induces vasodilation and protein extravasation, which is partly NO mediated, whereas CGRP-induced vasodilation appears to be NO independent.
|Digital Object Identifier (DOI):||doi:10.1159/000070707|
|Keywords:||neurogenic inflammation, microdialysis, laser doppler imaging, substance p, calcitonin gene-related peptide, erythema, endothelial permeability, wheal, flare|
|Subjects:||R Medicine > RL Dermatology
R Medicine > RM Therapeutics. Pharmacology
Q Science > QP Physiology
|Divisions :||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
|Accepted Date and Publication Date:||
|Date Deposited:||27 Apr 2006|
|Last Modified:||31 Mar 2016 11:50|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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