title: Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity.
abstract: This study investigated the interaction between exposure to air pollutants and chronic hypoxia (CH). We used a hypobaric chamber (14 days at barometric pressure 380 mmHg) to produce CH in rats. Exposure to various doses of acrolein or ozone did not modify the mechanical response to cholinergic agonists. Exposure to 3 microM/min acrolein did not alter epithelium-free trachea responsiveness. In contrast, direct exposure of freshly isolated myocytes to 2 and 3 microM/min acrolein enhanced the amplitude of the first intracellular [Ca(2+)] rise in response to 0.1 microM ACh and the calcium oscillation frequency in response to 10 microM ACh. CH alone did not alter smooth muscle cross-sectional area (SMA) or epithelium-plus-submucosa thickness. CH decreased maximal contractile response (maximal force normalized to SMA) but increased sensitivity (pEC(50)) to cholinergic agonists. We conclude that unlike in normoxic rats, exposure to air pollutants does not induce airway hyperresponsiveness in CH rats, although it increased calcium signaling. These results cannot be explained by change in smooth muscle accessibility, but may be linked to the effect of CH on calcium-contraction coupling.
authors.affiliation: Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et de la Recherche Médicale Equipe Mixte 9937, Université Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France. etienne.roux@u-bordeaux2.fr
authors.forename: Etienne
authors.initials: E
authors.lastname: Roux
authors.forename: Michel
authors.initials: M
authors.lastname: Duvert
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000171:Acrolein / Q000494:pharmacology; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002908:Chronic Disease; D005740:Gases / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D010083:Oxidants, Photochemical / Q000494:pharmacology; D010126:Ozone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000393:Air Pollutants; D018679:Cholinergic Agonists; D005740:Gases; D010083:Oxidants, Photochemical; D010126:Ozone; D000171:Acrolein; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium