Different mechanisms between thromboxane A2- and leukotriene D4-induced nasal blockage in guinea pigs.
Although thromboxane (TX)A2 is involved in allergic rhinitis, the mechanisms inducing nasal blockage have not been elucidated. We evaluated the roles of nasal mucosal vascular changes following intranasal instillation of the TXA2 analog U-46619 or leukotriene (LT)D4 to induce nasal blockage in a guinea pig model of allergic rhinitis. Both U-46619- and LTD4-induced nasal blockages in sensitized animals were swiftly and completely suppressed by a vasoconstrictor, naphazoline. The nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester relieved LTD4-induced nasal blockage, but not U-46619-induced nasal blockage. Although both agonists produced vasodilatation of nasal mucosa in vivo, LTD4 caused vasodilatation while U-46619 caused vasoconstriction in vitro. Both LTD4- and U-46619-induced nasal blockages in vivo should depend on vasodilatation of nasal mucosa. LTD4-induced nasal blockage is induced by direct vasodilatation via nitric oxide. In contrast, U-46619-induced nasal blockage may be associated with contraction of a certain vein that should exist at the exit of capacitance vessels, leading to congestion of the nasal mucosa.
Tanaka
Yoshiki
Y
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto, Japan.
Mizutani
Nobuaki
N
Fujii
Masanori
M
Nabe
Takeshi
T
Kohno
Shigekatsu
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology / Q000633:toxicity; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D006168:Guinea Pigs; D017998:Leukotriene D4 / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009278:Naphazoline / Q000494:pharmacology; D009297:Nasal Mucosa / Q000098:blood supply / Q000187:drug effects; D015508:Nasal Obstruction / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*
D010656:Phenylephrine; D009569:Nitric Oxide; D013928:Thromboxane A2; D017998:Leukotriene D4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009278:Naphazoline; D019331:NG-Nitroarginine Methyl Ester