Change in responsiveness of airway and beta-adrenoceptor in guinea pigs.
Allergen inhalation challenge resulted in significant (p < 0.05) increase in airway responsiveness to methacholine soon after immediate airway response (IAR) in guinea pigs actively sensitized with inhaled ovalbumin (OA) in vivo. We have investigated the involvement of thromboxane (Tx) A2 and platelet activating factor (PAF) in this airway hyperresponsiveness (AH). Pretreatment with CS-518, a selective thromboxane synthetase inhibitor, significantly inhibited both IAR (p < 0.07) and AH (p < 0.01), while pretreatment with WEB 2086, a PAF receptor antagonist, significantly inhibited only IAR (p < 0.05), but not AH after IAR. Propranolol, when inhaled before OA exposure, had no effect on bronchomotor tone, but if inhaled after IAR, it caused immediate death of guinea pigs. This result suggests that hyperresponsiveness of beta-adrenoceptor to propranolol may be induced by IAR. Examination of bronchoalveolar lavage (BAL) fluid revealed that no changes in cellular content were observed 60 min after OA exposure. In vitro, responsiveness of tracheal smooth muscle to carbachol was not changed by sensitization. Furthermore, anaphylactic reaction in vitro had no effect on the responsiveness. We conclude that airway responsiveness increases soon after IAR when infiltration of inflammatory cells is not yet found in vivo. It is also suggested that TxA2 but not PAF is involved in AH. Hyperresponsiveness to propranolol after IAR in OA sensitized guinea pigs illustrates the possibility of changes in function of beta-adrenoceptor after IAR.
First Department of Internal Medicine, School of Medicine, Showa University.
K
K
Minoguchi
M
M
Adachi
H
H
Tokunaga
Y
Y
Gonogami
Y
Y
Kouno
H
H
Kobayashi
K
K
Inoue
Y
Y
Sakai
I
I
Honma
T
T
Takahashi
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013928:Thromboxane A2 / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D013928:Thromboxane A2