Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs.
Acute exposure to cigarette smoke provokes bronchoconstriction and increases the concentration of thromboxane (Tx) A2 in bronchoalveolar lavage (BAL) fluid. The purpose of this study was to investigate the role of TxA2 and cholinergic mechanisms in the airway response induced by exposure to cigarette smoke in guinea-pigs. Anaesthetized animals were exposed to 200 puffs of smoke for 10 min. The amount of Evans blue dye extravasated into the bronchial tissue was then measured BAL was performed to determine cell counts and the concentration of TxB2, a stable metabolite of TxA2. The effects of pretreatment with a Tx synthase inhibitor, OKY-046 (10 mg.kg-1), and/or atropine (1 mg.kg-1) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction (284 +/- 33% of baseline pulmonary resistance (RL)) and plasma extravasation (30.0 +/- 3.8 vs 16.8 +/- 2.6 ng.mg-1 of sham control; main bronchi). OKY-046 or atropine significantly inhibited the bronchoconstriction to a similar extent, without affecting the plasma extravasation. Combined use of these compounds had no additive effect. The cigarette smoke caused significant increase in TxB2 (48 +/- 10 vs 14 +/- 1 pg.mL-1 of sham control) in BAL fluid, which was abolished by OKY-046 but not by atropine. The cellularity in BAL fluid was not different among groups. These results suggest that the bronchoconstriction induced by cigarette smoke is partially mediated by thromboxane A2, which is dependent on a cholinergic pathway.
Matsumoto
K
K
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aizawa
H
H
Inoue
H
H
Takata
S
S
Shigyo
M
M
Hara
N
N
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000294:innervation; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016084:Bronchoconstriction / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000032:analysis / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014026:Nicotiana
D004791:Enzyme Inhibitors; D008689:Methacrylates; D012906:Smoke; D013929:Thromboxane B2; D013928:Thromboxane A2; D001285:Atropine; D013930:Thromboxane-A Synthase; C034364:ozagrel