Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms after antigen challenge in sensitized guinea pigs.
To define the role of thromboxane A2 (TxA2) in allergic rhinitis, we examined the effects of the TxA2 receptor antagonist Bay u 3405 (1, 3 and 10 mg/kg, orally) on nasal symptoms, changes in total airway resistance (TAR), histamine hypersensitivity and eosinophil infiltration into the nasal mucosa induced by topical antigen challenge in actively sensitized guinea pigs. Nasal symptoms (number of sneezes and scratches) were significantly inhibited by pretreatment with Bay u 3405, in a dose-dependent manner. We noted a biphasic increase in TAR after antigen challenge. The first peak response of TAR (177.5 +/- 6.1%, mean +/- SE) was partially but significantly inhibited by Bay u 3405 at 10 mg/kg (142.8 +/- 4.3%, p < 0.01). The second peak response of TAR (181.0 +/- 13.4%) was also inhibited by Bay u 3405 at 3 mg/kg (120.3 +/- 3.1%) and 10 mg/kg (125.2 +/- 9.4%) (both, p < 0.01). The histamine hypersensitivity induced by antigen was inhibited by Bay u 3405 at 15 mg/kg (p < 0.05). Moreover, the mean eosinophil infiltration into the nasal mucosa induced by antigen (644.1 +/- 202.6/both sides of the nasal septum) was inhibited to 137.8 +/- 69.0 by Bay u 3405 at 10 mg/kg (p < 0.05). In conclusion, our results suggest that TxA2 may play an important role in allergic rhinitis in guinea pig models.
Narita
S
S
Department of Otolaryngology, Sapporo Medical University, Japan.
Asakura
K
K
Kataura
A
A
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D002227:Carbazoles / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000276:immunology; D006967:Hypersensitivity / Q000188:drug therapy; D007114:Immunization; D008297:Male; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012221:Rhinitis, Allergic, Perennial / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*
D000941:Antigens; D002227:Carbazoles; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D006632:Histamine; C063119:ramatroban