title: Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle.
abstract: Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
authors.forename: C
authors.initials: C
authors.lastname: Vannier
authors.forename: T L
authors.initials: TL
authors.lastname: Croxton
authors.forename: L S
authors.initials: LS
authors.lastname: Farley
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D002217:Carbachol; D009543:Nifedipine; D002118:Calcium