Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice.
The immediate responses of the upper respiratory tract (URT) to the irritants acrolein and acetic acid were examined in healthy and allergic airway-diseased C57Bl/6J mice. Acrolein (1.1 ppm) and acetic acid (330 ppm) vapors induced an immediate increase in flow resistance, as measured in the surgically isolated URT of urethane-anesthetized healthy animals. Acrolein, but not acetic acid, induced a small URT vasodilatory response. In awake spontaneously breathing mice, both vapors induced a prolonged pause at the start of expiration (a response mediated via stimulation of nasal trigeminal nerves) and an increase in total respiratory specific airway flow resistance, the magnitude of which was similar to that observed in the isolated URT. Both responses were significantly reduced in animals pretreated with large doses of capsaicin to defunctionalize sensory nerves, strongly suggesting a role for sensory nerves in development of these responses. The breathing pattern and/or obstructive responses were enhanced in mice with ovalbumin-induced allergic airway disease. These results suggest that the primary responses to acrolein and acetic acid vapors are altered breathing patterns and airway obstruction, that sensory nerves play an important role in these responses, and that these responses are enhanced in animals with allergic airway disease.
Morris
John B
JB
University of Connecticut Pulmonary Research Consortium, Department of Pharmaceutical Sciences, Storrs, Connecticut 06269, USA. morris@uconnvm.uconn.edu
Symanowicz
Peter T
PT
Olsen
Joshua E
JE
Thrall
Roger S
RS
Cloutier
Michelle M
MM
Hubbard
Andrea K
AK
D019342:Acetic Acid / Q000008:administration & dosage; D000171:Acrolein / Q000008:administration & dosage; D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000139:chemically induced; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D007509:Irritants / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology; D012123:Pulmonary Ventilation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000098:blood supply / Q000187:drug effects; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000503:physiopathology*; D014664:Vasodilation
D007509:Irritants; D000171:Acrolein; D010047:Ovalbumin; D019342:Acetic Acid