Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

Stephen E McGowan; Amey Jo Holmes; Jennifer Smith

doi:10.1152/ajplung.00158.2003

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Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

Journal article

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Peer reviewed

Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

Stephen E McGowan, Amey Jo Holmes and Jennifer Smith

American journal of physiology. Lung cellular and molecular physiology, Vol.286(2), pp.L437-444

02/2004

DOI: 10.1152/ajplung.00158.2003

PMID: 14711804

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Abstract

Airway hyperresponsiveness (AHR) is influenced by structural components of the bronchial wall, including the smooth muscle and connective tissue elements and the neuromuscular function. AHR is also influenced by parenchymally derived tethering forces on the bronchial wall, which maintain airway caliber by producing outward radial traction. Our previous work has shown that vitamin A-deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in the expression and function of the muscarinic-2 receptors (M2R). We hypothesized that if decreases in radial traction from airway or parenchymal structures contributed to the VAD-related increase in AHR, then the radial traction would normalize more slowly than VAD-related alterations in neurotransmitter signaling. Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained on the VAD diet in the presence or absence of supplementation with all-trans retinoic acid (RA). VAD was associated with an approximately twofold increase in respiratory resistance and elastance compared with VAS rats. Exposure to RA for 12 days but not 4 days restored resistance and elastance to control (VAS) levels. In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression and function, which were restored after 12 days of RA supplementation. Subepithelial bronchial elastic fibers were decreased by approximately 50% in VAD rats and were significantly restored by RA. The increase in AHR that is associated with VAD is accompanied by decreases in M2R expression and function that can be restored by RA and a reduction in airway elastic fibers that can be partially restored by RA.

Gene Expression

Elasticity

Bronchial Hyperreactivity - etiology

Receptor, Muscarinic M2 - genetics

Specific Pathogen-Free Organisms

Receptor, Muscarinic M2 - metabolism

Muscarinic Agonists - pharmacology

Bronchial Hyperreactivity - drug therapy

Vitamin A Deficiency - complications

Rats, Inbred Lew

Pulmonary Alveoli - physiology

Rats

Vitamin A Deficiency - physiopathology

Animals

Methacholine Chloride - pharmacology

Pilocarpine - pharmacology

Pulmonary Alveoli - drug effects

Female

Antineoplastic Agents - pharmacology

Bronchoconstrictor Agents - pharmacology

Tretinoin - pharmacology

Details

Title: Subtitle: Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency
Creators: Stephen E McGowan - Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242, USA. stephen-mcgowan@uiowa.edu
Amey Jo Holmes
Jennifer Smith
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.286(2), pp.L437-444
DOI: 10.1152/ajplung.00158.2003
PMID: 14711804
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: United States
Grant note: HL-53430 / NHLBI NIH HHS
Language: English
Date published: 02/2004
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983984518002771

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