ESSENTIAL ROLE FOR NITRIC-OXIDE IN NEUROGENIC INFLAMMATION IN RAT CUTANEOUS MICROCIRCULATION - EVIDENCE FOR AN ENDOTHELIUM-INDEPENDENT MECHANISM

The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the sa phenous nerve, was investigated by using two NO synthase inhibitors, N -G-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 neurogen ic edema as measured by I-125-albumin accumulation, whereas D-NAME (in active enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicte d vasopressor effect (before, 115+/-18 mm Hg; 5 minutes after, 174+/-1 8 mm Hg; n=6; P<.05), whereas 7-NI showed no significant increase in b lood 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 vasodilat or 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 e dema produced by stimulation of the saphenous nerve, it is suggested t hat release of NO is involved in neurogenic edema formation, but the v asodilator action of NO is unimportant in this context. We suggest tha t NO is involved in the release of neuropeptides from sensory nerves.