Vitamin A deficiency promotes bronchial hyperreactivity in rats by altering muscarinic M₂ 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.

Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice

“…A link between VAD and increased airway responsiveness had been previously reported in adult rats exposed to a prolonged VAD diet after weaning (61). The airway hyperresponsiveness was attributed to the reduced expression and function of muscarinic acetylcholine receptor M 2 (Chrm2) and decreased elastic fibers in the interstitium, but there was no structural defect in the airway SM.…”

Supplementation with vitamin A early in life and subsequent risk of asthma

“…Animal studies have shown that vitamin A deficiency promotes airway hyperresponsiveness and alters the mechanical properties of the lung parenchyma. Vitamin A deficiency is also associated with a reduced abundance and function of muscarinic M 2 receptors, which may help explain the diminished ability to limit cholinergic-mediated bronchoconstriction [19]. While supplementation with retinoic acid reverses the vitamin A deficiency-induced airway hyperresponsiveness and the decrease in muscarinic M 2 receptors [20], it does not appear to reverse alterations in parenchymal mechanics and structure resulting from vitamin A deficiency [42].…”

“…We recently reported that offspring born to mothers who received vitamin A before, during and after pregnancy as part of a randomised trial had better lung function than did those whose mothers received placebo [18]. Animal experiments have identified that vitamin A deficiency is associated with airway hyperresponsiveness [19] and that supplementation with all-trans retinoic acid, an active metabolic intermediate of vitamin A, reverses airway hyperresponsiveness associated with vitamin A deficiency [20]. While multiple observational studies [21][22][23][24][25] have found that vitamin A deficiency is associated with a higher risk of asthma, there are no randomised trials to support a causal relationship.…”

Asthma in the 21st Century — Unexpected Applications of Ancient Treatments

“…Mechanistically, vitamin A may regulate bronchial hyperreactivity by altering the function and abundance of the muscarinic M(2) receptors in bronchial tissue [203]. Moreover, carotenoids may regulate activation of a variety of transcription factors.…”