Abnormal modulation of cholinergic neurotransmission by endogenous nitric oxide in the bronchus of rats with hyperresponsiveness induced by allergen challenge.
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.
Misawa
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Sato
J
J
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002799:Cholinergic Fibers / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000485:Allergens; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003995:Dibutyryl Cyclic GMP; D000109:Acetylcholine