CUTANEOUS VASODILATATION INDUCED BY NITRIC OXIDE-EVOKED STIMULATION OF AFFERENT NERVES IN THE RAT

1 The site of action at which nitric oxide (NO) may contribute to neurogenic vasodilatation in the hindpaw skin of urethane-anaesthetized rats was examined by the use of N-G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. 2 Skin blood flow was measured by laser Doppler flowmetry, and neurogenic vasodilatation was evoked either by topical application of mustard oil (5%) or antidromic electrical stimulation of the saphenous nerve (antidromic vasodilatation). 3 L-NAME (60 mu mol kg(-1), i.v.) attenuated the hyperaemia evoked by mustard oil in an enantiomer-specific manner but failed to reduce antidromic vasodilatation and the vasodilatation due to i.v. injected calcitonin gene-related peptide (CGRP) and substance P (O.1-1 nmol kg(-1) each), two proposed mediators of neurogenic vasodilatation. 4 Pretreatment of rats with capsaicin (125 mg kg(-1), s.c. 2 weeks beforehand), to defunctionalize afferent neurones, reduced the hyperaemic response to mustard oil and prevented L-NAME from further decreasing the vasodilatation evoked by mustard oil. 5 Intraplantar infusion of sodium nitroprusside (SNP, 0.15 nmol in 1 min), a donor of NO, induced hyperaemia which was significantly diminished by the CGRP antagonist CGRP(8-37) (50 nmol kg(-1), i.v.) and by capsaicin pretreatment. The ability of CGRP(8-37), to inhibit the vasodilator response to SNP was lost in capsaicin-pretreated rats. 6 Taken together, these data indicate that NO does not play a vasorelaxant messenger role in neurogenic vasodilatation but can contribute to activation of, and/or transmitter release from, afferent nerve fibres in response to irritant chemicals.