Capsaicin pretreatment inhibits vagal cholinergic and non-cholinergic control of pulmonary mechanics in the guinea pig

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Abstract
The effects of vagal nerve stimulation, ether, capsaicin, histamine and substance P (SP) on lung resistance (R1) and dynamic lung compliance (CDYN) were studied in anaesthetized guinea pigs. The in vivo responses in control animals were compared with the effects after systemic pretreatment with capsaicin or local application of capsaicin on the cervical vagal nerves. Vagal nerve stimulation induced an increase in RL and a fall in CDYN. Significant changes in RL and DDYN (more than 50%) were still present after atropine, while the vagal heart response was abolished. Systemic or local capsaicin pretreatment abolished the atropine-resistant vagal effect on RL and CDYN. The atropine-sensitive changes in pulmonary mechanics upon vagal stimulation were significantly reduced by capsaicin pretreatment. The increase in RL and a fall in CDYN induced by ether and capsaicin was significantly reduced or abolished by systemic capsaicin pretreatment, while the histamine-induced bronchoconstriction was only slightly reduced. Ether and capsaicin seemed also to activate capsaicin-sensitive neurons of non-vagal origin since they still caused large effects in animals, which has been locally pretreated with capsaicin on the vagal nerves. The increased RL and decreased CDYN induced by SP was unchanged in capsaicin-pretreated animals. The tracheal tension increase in vitro induced by acetylcholine and histamine was uninfluenced by systemic capsaicin pretreatment. The atropine-sensitive tracheal contraction and atropine-resistant relaxation upon field stimulation seemed also to be unchanged after capsaicin pretreatment. Choline-acetyltransferase activity and muscarinic receptor-binding characteristics (affinity and number of receptor sites) in the trachea and lung of the guinea pig and rat were found to be unchanged after systemic capsaicin pretreatment. In conclusion, capsaicin pretreatment abolishes the non-cholinergic vagal changes in RL and CDYN. However, the vagal cholinergic control of pulmonary mechanics was partially inhibited by capsaicin pretreatment. This seemed to occur via mechanisms not involving degeneration of cholinergic nerves or major changes in muscarinic receptor function.