Neurogenic oedema and vasodilatation: effect of a selective neuronal NO inhibitor.
The effects of a neuronal nitric oxide synthase (nNOS) inhibitor, 1-(2-trifluoromethylphenyl)imidazole (TRIM) on rat sensory saphenous nerve-induced neurogenic inflammation were investigated. TRIM (50 mg kg-1, i.p.), but not 2-trifluoromethylphenol (TRIMPOH) which lacks nNOS inhibitory activity, inhibited neurogenic oedema by 55.8 +/- 6.5% (n = 6, p < 0.05). The effect of TRIM was partially reversed by L-arginine (100 mg kg-1, i.v., p < 0.01). TRIM also caused a reduction (p < 0.05) in neurogenic vasodilatation but had no effect on neuropeptide responses induced by substance P + CGRP. Topically applied TRIM (100 microliters of 150-250 mg ml-1) inhibited neurogenic oedema (p < 0.01). Thus, use of this recently described nNOS inhibitor has provided new evidence to further the hypothesis that nNOS plays a role in modulating sensory nerve-mediated neurogenic inflammation.
Towler
P K
PK
Division of Biomedical Sciences, Kings College London, UK.
Bennett
G S
GS
Moore
P K
PK
Brain
S D
SD
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006614:Hindlimb; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
C113796:2-trifluoromethylphenol; D004791:Enzyme Inhibitors; D006845:Hydrocarbons, Fluorinated; D007093:Imidazoles; D010636:Phenols; D014662:Vasoconstrictor Agents; C098186:1-(2-trifluoromethylphenyl)imidazole; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat