Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D-4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B-1 receptor antagonist, des-Arg(9)-[Leu(8)]bradykinin nor a bradykinin B-2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D-4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D-4 was developed by a bradykinin B-2 receptor agonist, bradykinin, but not by a bradykinin B-1 receptor agonist, des-Arg(10)-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B-2 but also B-1 receptors. (C) 2003 Elsevier B.V. All rights reserved.