Abstract
BackgroundBronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD) is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA) or remained unsupplemented.MethodsParenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh) by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion.ResultsVAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS) rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment.ConclusionAlterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.
Highlights
Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways
In order to better identify the mechanisms that are responsible for airway hyperreactivity in vitamin A deficiency (VAD) rats, with respect to morphological and biochemical characteristics of the pulmonary elastic fiber network, we evaluated the mechanical properties of the lung parenchyma that are most involved in regulating small airway diameter
The elastance of excised lungs that were ventilated at a tidal volume of 0.3 ml and 3 cm positive end expiratory pressure (PEEP) was significantly higher in VAD than in vitamin A sufficient (VAS) rats in the absence of CCh (Figure 1)
Summary
Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. In our experimental model of VAD, rats do not become deficient until after the period of maximal alveolar formation, which is completed by 3 weeks of age [2,6]. During these first 3 weeks of postnatal life there is an increase in the mRNA for tropoelastin, the soluble precursor of cross-linked elastin, which is an important determinant of the mechanical properties of the lung parenchyma and airways [7]. Once it is cross-linked, elastin normally undergoes very little turnover, this does occur in pathological conditions such as emphysema [6,8]
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