Abnormal Modulation of Cholinergic Neurotransmission by Endogenous Nitric Oxide in the Bronchus of Rats with Hyperresponsiveness Induced by Allergen Challenge

[摘要] References(21)The involvement of endogenous nitric oxide (NO)in bronchial cholinergic neurotransmission was compared between normal rats and airway hyperresponsive (AHR)rats. Male Wistar rats were sensitized and repeatedly challenged with dinitrophenylated (DNP)-Ascaris antigen. Twenty-four hours after the last antigenic challenge, enhancements of both the electrical field stimulation (EFS)-induced bronchoconstriction and acetylcholine (ACh)release were observed. NG-Monomethyl-L-arginine (L-NMMA; NO synthase inhibitor, 0.1 mM)augmented the EFS-induced bronchoconstriction and ACh release without affecting exogenously applied ACh-induced bronchoconstriction in normal rats. Interestingly, the augmentative effects of L-NMMA seen in normal rats were not manifested in AHR rats. Sodium nitroprusside inhibited the EFS-induced bronchoconstriction in a concentration-dependent manner; the inhibition was much larger than that of exogenously applied ACh-induced constriction in both normal and AHR rats. Furthermore, dibutyryl cGMP (3 mM)inhibited the EFS-induced bronchoconstriction with no effect on the ACh-induced bronchoconstriction in both normal and AHR rats. These findings suggest that endogenous NO may have a modulatory role in bronchial cholinergic neurotransmission in normal rats and that the augmented ACh release in the AHR rats may result from the defect of endogenous NO-induced modulation of cholinergic nerve transmission.

[学科分类] 药理学

[关键词] Airway hyperresponsiveness;Nitric oxide;Cholinergic neurotransmission;Nitrergic dysfunction;Dinitrophenylated (DNP)-Ascaris