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Essential Role for Nitric Oxide in Neurogenic Inflammation in Rat Cutaneous Microcirculation
Evidence for an Endothelium-Independent Mechanism
From the Pharmacology Group and Vascular Biology Research Centre, Division of Biomedical Sciences, King's College, London, UK.
Correspondence to Dr S.D. Brain, Pharmacology Group and Vascular Biology Research Centre, Division of Biomedical Sciences, King's College, Manresa Road, London SW3 6LX, UK.
Abstract The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both L-NAME (100 mg/kg IV, P<.05) and 7-NI (10 mg/kg IV, P<.05) caused an L-arginine (100 mg/kg IV, P<.01)–reversible inhibition of neurogenic edema as measured by 125I-albumin accumulation, whereas D-NAME (inactive enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicted vasopressor effect (before, 115±18 mm Hg; 5 minutes after, 174±18 mm Hg; n=6; P<.05), whereas 7-NI showed no significant increase in blood pressure (before, 96±9 mm Hg; 5 minutes after, 102±10 mm Hg; n=6), and neither L-NAME nor 7-NI had any effect on basal or vasodilator calcitonin gene-related peptide (CGRP, 10 pmol per site)–stimulated local blood flow in rat skin, as measured by laser Doppler flowmetry. Furthermore, systemic and local 7-NI had no effect on edema formation induced by local administration of substance P (with or without CGRP) and histamine (with or without CGRP) in rat skin. Since 7-NI blocks edema produced by stimulation of the saphenous nerve, it is suggested that release of NO is involved in neurogenic edema formation, but the vasodilator action of NO is unimportant in this context. We suggest that NO is involved in the release of neuropeptides from sensory nerves.
Key Words: neurogenic inflammation • nitric oxide • substance P • calcitonin gene-related peptide • sensory nerves
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