Published ahead of print on February 5, 2003, doi:10.1164/rccm.200201-055OC
© 2003 American Thoracic Society
Neurokinins Modulate Hyperventilation-induced Bronchoconstriction in Canine Peripheral AirwaysDepartment of Environmental Health Sciences, School of Public Health, The Johns Hopkins University, Baltimore, Maryland Correspondence and requests for reprints should be addressed to Arthur N. Freed, National Heart, Lung, and Blood Institute, Two Rockledge Center, Suite 7186, 6701 Rockledge Drive, Bethesda, MD 20892–7924. E-Mail: freeda{at}nhlbi.nih.gov This study was designed to test the hypotheses that (1) neurokinin (NK) receptor activity modulates hyperventilation-induced bronchoconstriction (HIB) in canine peripheral airways and (2) NK receptor activity is stimulated via hyperventilation-induced eicosanoid production and release. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance (Rp); to test airway reactivity to NK A (NKA), substance P, and hypertonic saline; and to examine HIB before and after combined treatment with NK-1 (CP 99,994) and NK-2 (SR 48,968) receptor antagonists. Bronchoalveolar lavage fluid cells, prostaglandin D2, and cysteinyl leukotrienes from hyperventilated airways pretreated with either vehicle or NK antagonists were also measured. Pretreatment with NK-1 and NK-2 antagonists significantly attenuated HIB and the response to substance P, virtually abolished the response to NKA, and had little effect on the response to HS. Blockade of NK-1 and NK-2 receptors did not affect either the cell profiles or the mediator concentrations recovered in bronchoalveolar lavage fluid after hyperventilation. We conclude that NKs modulate the development of HIB and appear to do so via hyperventilation-induced eicosanoid production and release.
Key Words: animal model • exercise-induced asthma • neurokinins This article has been cited by other articles:
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