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Cutaneous vasodilatation induced by nitric oxide‐evoked stimulation of afferent nerves in the rat
Author(s) -
Holzer P.,
Jocič M.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13208.x
Subject(s) - calcitonin gene related peptide , vasodilation , antidromic , capsaicin , sodium nitroprusside , nitric oxide , chemistry , neurogenic inflammation , stimulation , endocrinology , anesthesia , medicine , hyperaemia , pharmacology , neuropeptide , substance p , blood flow , receptor
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 μmol 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 (0.1–1 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.