Studies on the role of the autonomic nervous system in airway hyperreactivity.

The airway hyperreactivity (AH) characteristic of bronchial asthma has many possible underlying causes. This study focussed on the contribution of K+ -ion channels and Ca2+ - dependent processes to AH, in a guinea-pig model of asthma. Cromakalim, a potassium channel opening drug, attenuated vagally-mediated constriction in vitro in both normal and sensitized guinea-pig trachea, suggesting that the pre-junctional K+ - channels involved in modulating vagal tone are functioning normally in sensitized tissues. The sensitization process however, may alter post-junctional K+ - channel behaviour since cromakalim attenuated responses only to lower concentrations of exogenously applied acetylcholine (ACh) in sensitized trachea. The voltage-dependent Ca2+ - channel (VDC) blocking drugs, verapamil and nifedipine, attenuated responses to applied ACh and stimulation of the vagus nerve in untreated tissues, indicating significant VDC involvement in the production of spontaneous and evoked tone. The calmodulin antagonist, trifluoperazine (TFP), also reduced responses to applied ACh and vagal stimulation in normal guinea-pigs. In sensitized trachea, verapamil was less effective against vagally-induced tone suggesting that changes in pre-junctional Ca2+ - channels are involved. TFP, however, was less effective against ACh-induced constriction in sensitized trachea, which implies that calmodulin-mediated mechanisms in the trachealis are altered after sensitization. Vagal bronchoconstriction was attenuated in vivo by cromakalim in untreated and sensitized animals to the same degree but no direct bronchodilator effect was apparent. Verapamil and TFP also attenuated vagally-mediated responses in sensitized and unsensitized animals to the same extent. Thus the altered responsiveness to drugs observed in vitro in sensitized trachea was not evident in vivo, suggesting that additional neural and/or humoral factors may interact to mask in vitro effects. These results strongly support the theory that sensitization alters the normal functioning of K+ and Ca2+ ion channels and intracellular Ca2+ handling and that these changes could contribute to vagal hyperresponsiveness and AH in general.

Grantor dc:publisher.institution

Robert Gordon University

Year dc:date.issued

1993

Author dc:creator

• De Jonckheere, Susan

Advisor dc:contributor.advisor

• D. McCaig

• Autonomic nervous system
• Airway hyperreactivity
• Bronchial asthma
• Cromakalim
• Trachealis
• Sensitization
• Verapamil
• Nifedipine

Language dc:language

en

Identifier

oai:rgu-repository.worktribe.com:2807357
https://doi.org/10.48526/rgu-wt-2807357

OAI identifier oai:identifier

oai:rgu-repository.worktribe.com:2807357