Augmented venous responsiveness to leukotriene D(4) in nasal septal mucosae of repeatedly antigen-challenged rats.
One possible mechanism of the nasal obstruction observed in allergic rhinitis is thought to be a dilatation of veins in nasal mucosa, although the exact mechanism(s) is not fully understood. An involvement of cysteinyl leukotrienes (CysLTs) in the nasal obstruction has also been suggested. In addition to the specific antigen-induced nasal symptoms, nasal hyperresponsiveness to non-specific stimuli is one of the characteristic features of patients with allergic rhinitis. Augmentation of LTD(4)-induced venodilatation (a part of nasal hyperresponsiveness) of nasal mucosae in antigen-challenged rats was investigated. The LTD(4)-induced venodilatation was significantly increased in antigen-challenged rats, although venodilatation by application of LTD(4) was not induced in nasal mucosae of control rats. The LTD(4)-induced venodilatation was significantly inhibited by pretreatment with L-NMMA [an inhibitor of nitrix oxide synthase (NOS)]. Although mRNA of CysLT1 receptor of nasal mucosa was within control level, the LTD(4)-induced production of NOx in nasal cavity was augmented in repeatedly antigen challenge rats. In addition, the level of iNOS mRNA was also significantly augmented in nasal mucosae of repeatedly antigen-challenged rats. Interestingly, sodium nitroprusside (SNP; an NO donor)-induced venodilatation itself was significantly augmented in nasal mucosae of repeatedly antigen challenge rats. In conclusion, we here suggest that the sensitivity of venodilatation to LTD(4) was augmented in nasal mucosae of challenged rats. Therein, not only increased NO production but also enhanced NO responsiveness might be involved in the development of nasal hyperresponsiveness in allergic rhinitis.
Sakai
Hiroyasu
H
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. sakai@hoshi.ac.jp
Enzaka
Jun
J
Sakai-Oshita
Michiko
M
Chiba
Yoshihiko
Y
Misawa
Miwa
M
D000818:Animals; D000941:Antigens / Q000276:immunology; D003545:Cysteine / Q000276:immunology; D017998:Leukotriene D4 / Q000276:immunology*; D015289:Leukotrienes / Q000276:immunology; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018077:Receptors, Leukotriene / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D014664:Vasodilation / Q000276:immunology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000941:Antigens; D015289:Leukotrienes; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; C112381:cysteinyl-leukotriene; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D017998:Leukotriene D4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D003545:Cysteine; C083169:leukotriene D4 receptor