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 neur ogenic vasodilatation in the hindpaw skin of urethane-anaesthetized ra ts was examined by the use of N-G-nitro-L-arginine methyl ester (L-NAM E), an inhibitor of NO synthase. 2 Skin blood flow was measured by las er Doppler flowmetry, and neurogenic vasodilatation was evoked either by topical application of mustard oil (5%) or antidromic electrical st imulation 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 v asodilatation and the vasodilatation due to i.v. injected calcitonin g ene-related peptide (CGRP) and substance P (O.1-1 nmol kg(-1) each), t wo proposed mediators of neurogenic vasodilatation. 4 Pretreatment of rats with capsaicin (125 mg kg(-1), s.c. 2 weeks beforehand), to defun ctionalize afferent neurones, reduced the hyperaemic response to musta rd oil and prevented L-NAME from further decreasing the vasodilatation evoked by mustard oil. 5 Intraplantar infusion of sodium nitroprussid e (SNP, 0.15 nmol in 1 min), a donor of NO, induced hyperaemia which w as 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-pr etreated rats. 6 Taken together, these data indicate that NO does not play a vasorelaxant messenger role in neurogenic vasodilatation but ca n contribute to activation of, and/or transmitter release from, affere nt nerve fibres in response to irritant chemicals.