Passive smoke effects on cough and airways in young guinea pigs: role of brainstem substance P.
Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid-induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid-induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid-induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.
Joad
Jesse P
JP
Department of Pediatrics, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA. jpjoad@ucdavis.edu
Munch
Paul A
PA
Bric
John M
JM
Evans
Samuel J
SJ
Pinkerton
Kent E
KE
Chen
Chao-Yin
CY
Bonham
Ann C
AC
D000336:Aerosols; D000367:Age Factors; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D016084:Bronchoconstriction / Q000502:physiology*; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D006168:Guinea Pigs; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007267:Injections; D008168:Lung / Q000294:innervation; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000502:physiology; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000336:Aerosols; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D014028:Tobacco Smoke Pollution; D006710:Homocysteine; C007956:homocysteic acid; C085215:SR 140333; D019343:Citric Acid; D013373:Substance P