title: Neurokinins modulate hyperventilation-induced bronchoconstriction in canine peripheral airways.
abstract: 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.
authors.affiliation: Department of Environmental Heatlh Sciences, School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA. freeda@nhlbi.nih.gov
authors.forename: Arthur N
authors.initials: AN
authors.lastname: Freed
authors.forename: Sharron
authors.initials: S
authors.lastname: McCulloch
authors.forename: Teresa
authors.initials: T
authors.lastname: Meyers
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology*; D016084:Bronchoconstriction; D004285:Dogs; D015777:Eicosanoids / Q000096:biosynthesis / Q000378:metabolism; D006985:Hyperventilation / Q000276:immunology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000502:physiology*
chemical_list: D015777:Eicosanoids; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2