The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester on neuropeptide-induced vasodilation and protein extravasation in human skin.
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 x 10(-7)M and 2 x 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 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(-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 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.
Klede
Monika
M
Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nürnberg, Erlangen, Germany.
Clough
Geraldine
G
Lischetzki
Grischa
G
Schmelz
Martin
M
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage*; D003872:Dermatitis / Q000276:immunology; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004890:Erythema / Q000139:chemically induced / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009619:Nociceptors / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000294:innervation; D013373:Substance P / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects*
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester