title: Vitamin A deficiency promotes bronchial hyperreactivity in rats by altering muscarinic M(2) receptor function.
abstract: Vitamin A deficiency (VAD) remains an important health problem among children in developing countries. Children living in these areas have a higher mortality from respiratory infections, which likely results in part from suboptimal nutrition, including VAD. Bronchial hyperreactivity can follow viral respiratory infections and may complicate the recovery. To investigate whether VAD promotes bronchial hyperreactivity, we have assessed methacholine-induced bronchoconstriction in VAD and vitamin A-sufficient rats. Bronchial constriction developed at lower concentrations of inhaled methacholine in VAD than in vitamin A-sufficient rats. This did not result from an increase in the bronchial wall thickness or the clearance of a small molecule (with a size similar to methacholine) from the air space. The function and abundance of the muscarinic M(2) receptors in bronchial tissue were reduced in VAD rats, suggesting that this receptor may contribute to these animals' diminished ability to limit cholinergic-mediated bronchoconstriction. A similar reduction in muscarinic M(2) receptor function has been observed in asthma. Vitamin A (retinol) and its congeners (retinoids) may be required to regulate bronchial responsiveness in addition to maintaining a normal bronchial epithelium.
authors.affiliation: Department of Veterans Affairs Research Service, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. stephen-mcgowan@uiowa.edu
authors.forename: Stephen E
authors.initials: SE
authors.lastname: McGowan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.forename: Amey Jo
authors.initials: AJ
authors.lastname: Holmes
authors.forename: Lori A
authors.initials: LA
authors.lastname: Smith
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Businga
authors.forename: Mark T
authors.initials: MT
authors.lastname: Madsen
authors.forename: Ulla C
authors.initials: UC
authors.lastname: Kopp
authors.forename: Joel N
authors.initials: JN
authors.lastname: Kline
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000737:chemistry / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D003243:Consciousness; D005260:Female; D016210:Methacholine Chloride / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000032:analysis / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D014802:Vitamin A Deficiency / Q000503:physiopathology*
chemical_list: D016085:Bronchoconstrictor Agents; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D016284:Technetium Tc 99m Pentetate