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 NG-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 mumol 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 CGRP8-37 (50 nmol kg-1, i.v.) and by capsaicin pretreatment. The ability of CGRP8-37 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.
Holzer
P
P
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Jocic
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester