Tachykinins do not cause plasma leakage in the rabbit trachea
Introduction
Tachykinins are neuropeptides which, in the airways, are primarily located in sensory nerve endings or C-fibers. The most frequently studied sensory neuropeptides are substance P and neurokinin A. These peptides have been found in the airways of many species and have been shown to provoke numerous responses including bronchoconstriction and increases in both microvascular leakage and mucus secretion (Barnes et al., 1991). However, species differences exist with respect to the amount of sensory neuropeptide present, receptor location, response to receptor stimulation (Martling, 1987), the presence of neuropeptide degradative enzymes (Funayama et al., 1994) and subsequently the physiological effect of exogenous application of these peptides.
In rabbits, neuropeptide receptors are present throughout the airways although the presence of the substance P receptor (neurokinin 1, NK1) increases significantly peripherally. In vitro, exogenous neuropeptides contract airway smooth muscle (Black et al., 1990) and in vivo increase mucociliary activity, at least in the maxillary sinus (Lindberg and Dolata, 1993). In both the guinea pig and rat airways neuropeptides (primarily substance P) are important mediators of increases in microvascular leakage. This response has not been reported in the airways of the rabbit.
To examine the role that neuropeptides play in increases in airway microvascular leakage in the rabbit we determined the effect of vagal stimulation, treatment with the neurotoxin capsaicin (which selectively acts upon C-fibers inducing the release of neuropeptides) or exogenous substance P. Microvascular leakage was assessed using the Evans blue dye technique.
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Animals
All studies were approved by the Animal Ethics Committee of Royal North Shore Hospital. Studies were carried out on New Zealand white male rabbits weighing 2.5–3.5 kg, which were caged individually with free access to food and water prior to study.
Chemicals and drugs
The following chemicals were used: Evans blue, capsaicin, Tween 80 (Sigma, St. Louis, MO). The following drugs were used: xylazine (Bayer, NSW, Australia), ketamine (Troy NSW, Australia), pentobarbitone sodium (Boehringer Ingelheim, NSW, Australia)
Experiment 1: capsaicin
The control group treated with the solvent for capsaicin gave a baseline value of 28.5±9.0 μg Evans blue per gram trachea (Fig. 1). Treatment with capsaicin either subcutaneously (30.7±2.9) or intraperitoneally (32.7±5.0) had no significant effect on the baseline level of tracheal Evans blue concentration. Thiorphan, when given as a pretreatment to rabbits injected with capsaicin did not affect tracheal Evans blue concentration (31.4±7.1).
Experiments 2, 3 and 4
Metabisulphite (positive control, 80.0±14.8)
Discussion
The present study indicates that neuropeptides, either through endogenous release by capsaicin or vagal stimulation or by exogenous challenge, are not mediators of microvascular leakage in the major airways of the rabbit.
Increases in microvascular leakage, as a component of the inflammatory response, may significantly contribute to the pathogenesis of inflammatory airway diseases such as asthma. In the airways of rats and guinea pigs the locally acting neural reflex by which a stimulus induces
Acknowledgements
This work was supported by a grant from the National Health and Medical Research Council of Australia.
References (13)
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