The Effect of the Nitric Oxide Synthase Inhibitor N-Nitro- L-Arginine-Methyl Ester on Neuropeptide-Induced Vasodilation and Protein Extravasation in Human Skin

Abstract

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^–6 M) or calcitonin gene-related peptide (CGRP; 5 × 10^–7 M and 2 × 10^–6 M). 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 m M. L-NAME (5 m M) 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^–7 M SP and 30% for 10^–6 M 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 m M) 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.

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2003

Publication date (Print): April 2003

Publication date (Electronic): 19 June 2003

Volume: 40

Issue: 2

Pages: 105-114

Affiliations

Departments of ^aPhysiology and Experimental Pathophysiology, ^bPediatrics, University of Erlangen/Nürnberg, Erlangen, and ^cAnesthesiology Mannheim, University of Heidelberg, Heidelberg, Germany; ^dDepartment of Allergy and Inflammation Sciences, University of Southampton, Southampton, UK

Article

Publisher ID: 70707 Other ID: J Vasc Res 2003;40:105–114

DOI: 10.1159/000070707

PubMed ID: 12808346

Copyright statement: © 2003 S. Karger AG, Basel

License:

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Page count

Figures: 4, References: 56, Pages: 10

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Categories

Subject: Research Paper