Cigarette smoke-induced bronchoconstriction: cholinergic mechanisms, tachykinins, and cyclooxygenase products.
The mechanisms underlying cigarette smoke-induced bronchoconstriction were studied by using selective blockade of muscarinic acetylcholine receptors, neurokinin receptors and production of eicosanoids of the cyclooxygenase pathway in anesthetized guinea pigs. Inhalation of three breaths of cigarette smoke (University of Kentucky research series 2R1; 2.45 mg of nicotine and 35.3 mg of tar per cigarette) reproducibly induced an immediate bronchoconstriction; total pulmonary resistance increased from 0.24 +/- 0.02 to 1.44 +/- 0.21 cmH2O.ml-1.s (P < 0.01) and dynamic lung compliance decreased from 0.53 +/- 0.03 to 0.39 +/- 0.06 ml/cmH2O (P < 0.05) in 10-15 breaths after the smoke inhalation. Atropine pretreatment (50 micrograms/kg i.v.) prevented the immediate decrease in dynamic lung compliance and reduced the immediate increase in total pulmonary resistance by approximately 55%. The atropine-resistant bronchoconstriction occurring immediately after smoke inhalation was completely blocked by a pretreatment with a combination of CP-99994 (0.3 mg/kg i.v.) and SR-489668 (0.3 mg/kg i.v.), the antagonists of neurokinin-1 and neurokinin-2 receptors, respectively. However, a delayed and sustained bronchoconstriction still persisted and reached a plateau in 45-55 breaths after smoke inhalation challenge. This delayed response was completely prevented by pretreatment with indomethacin (5 mg/kg i.v.). We conclude that the smoke-induced bronchoconstriction in guinea pigs consists of an early phase induced by both a cholinergic reflex and tachykinin release, probably evoked by the activation of bronchopulmonary C fibers, and a late phase caused by the action of arachidonic acid metabolite(s) of the cyclooxygenase pathway.
Hong
J L
JL
Department of Physiology, University of Kentucky, Lexington 40536, USA.
Rodger
I W
IW
Lee
L Y
LY
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D002799:Cholinergic Fibers / Q000378:metabolism*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012119:Respiration; D012907:Smoking / Q000009:adverse effects*; D015320:Tachykinins / Q000378:metabolism*
D015320:Tachykinins; D009538:Nicotine; D001285:Atropine; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin