Increased expression of inducible nitric oxide synthase in nasal mucosae of guinea pigs with induced allergic rhinitis.
BACKGROUND
Nitric oxide (NO) is produced by the action of NO synthase (NOS) isoforms and is considered an important mediator of inflammatory response including airways. In this study, the changes in the expression levels of NOS isoforms in nasal mucosae were determined in a guinea pig model of allergic rhinitis.


METHODS
An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated ovalbumin antigen. Twenty-four hours after the last antigen challenge, the expression levels of NOS isoforms in nasal mucosae were determined by immunoblottings. Changes in the isometrical tension of isolated mucosal tissues of nasal septa induced by histamine were measured also.


RESULTS
Although the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in nasal mucosae were not affected by the repeated antigen exposure, the inducible NOS (iNOS) level was markedly and significantly increased in the challenged animals. In isolated nasal mucosal tissues, histamine induced a concentration-dependent relaxation, which was sensitive to an H1-receptor antagonist, mepyramine, and an NOS inhibitor, L-NMMA. No significant change in the histamine responsiveness was observed between the sensitized control and repeatedly antigen-challenged groups.


CONCLUSIONS
The expression of three isoforms of NOS, including eNOS, nNOS, and iNOS, was presented in guinea pig nasal mucosa. A marked increase in iNOS expression in the repeatedly antigen-challenged animals suggests an important role of iNOS in the pathogenesis of allergic rhinitis. However, the pathophysiological role(s) of NO generated by iNOS in nasal allergy is still unclear.
Chiba
Yoshihiko
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. chiba@hoshi.ac.jp
Matsuo
Kensuke
K
Sakai
Hiroyasu
H
Abe
Kazuho
K
Misawa
Miwa
M
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine / Q000032:analysis / Q000494:pharmacology; D018494:Histamine Agents / Q000032:analysis / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000201:enzymology*
D018494:Histamine Agents; D006632:Histamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III