Neuronal nitric oxide synthase-derived nitric oxide is involved in gastric mucosal hyperemic response to capsaicin in rats.
OBJECTIVE
Activation of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin leads to gastric hyperemic response through capsaicin-sensitive sensory nerves and nitric oxide (NO). The aim of the present study is to examine which isoform of nitric oxide synthase (NOS)/NO is involved in the hyperemic response to capsaicin in the rat stomach.


METHODS
Gastric mucosal blood flow (GMBF) was measured by laser Doppler flowmetry in rats. The localizations of TRPV1 and neuronal NOS (nNOS) in the rat gastric mucosa were detected by immunohistochemical staining.


RESULTS
The nNOS inhibitor N(5)-[imino(propylamino)methyl]-L-ornithine substantially reduced GMBF during capsaicin application, whereas the endothelial NOS (eNOS) inhibitor N(5)-(1-iminomethyl)-L-ornithine did not affect the effect of capsaicin during the application. The nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester apparently inhibited the capsaicin-induced GMBF, while the inducible NOS inhibitor 1400W did not affect GMBF response to capsaicin. The immunohistochemical studies revealed nerve fibers coexpressing TRPV1 and nNOS around blood vessels in the gastric submucosa.


CONCLUSIONS
We demonstrated for the first time that nNOS/NO is involved in gastric hyperemic responses to capsaicin.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Chiba, Japan.
Masaki
M
Raimura
Kimihito
K
Tashima
Kenjiro
K
Matsumoto
Shinya
S
Tobe
Atsushi
A
Chino
Takao
T
Namiki
Katsutoshi
K
Terasawa
Syunji
S
Horie
D000818:Animals; D002211:Capsaicin; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D006940:Hyperemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000378:metabolism
D004791:Enzyme Inhibitors; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester