REDUCED LUNG WATER TRANSPORT RATE ASSOCIATED WITH DOWNREGULATION OF AQUAPORIN-1 AND AQUAPORIN-5 IN AGED MICE |
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| Authors: | Ying-Wei Zhang Lin-Tao Bi Song-Ping Hou Xue-Liang Zhao Yuan-Lin Song Tong-Hui Ma |
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| Institution: | Membrane Channel Research Laboratory of Northeast Normal University,;China-Japan Union Hospital Affiliated to Jilin University, Changchun, PR China and;Department of Anesthesia, University of California San Francisco, San Francisco, California, USA |
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| Abstract: | - 1 The purpose of the present study was to examine lung water transport properties and the expression and regulation of the alveolar endothelial water channel aquaporin (AQP)‐1 and the epithelial water channel AQP‐5 in aged mouse lung using gene expression analysis and water permeability measurements.
- 2 In aged (20–24‐month‐old) mice, AQP‐1 and AQP‐5 mRNA expression decreased by 55.5 and 50.3%, respectively, compared with that in young (8–10‐week‐old) mice (P < 0.01). In addition, AQP‐1 and AQP‐5 protein expression decreased in aged mice by 36.9 and 44.6%, respectively, compared with that in young mice (P < 0.01).
- 3 The osmotically driven water transport rate between the airspace and capillary compartments was reduced by 31.7% in aged mice compared with young mice (2.8 ± 0.3 vs 4.1 ± 0.3 mg/s, respectively; P < 0.01). The hydrostatically driven lung water accumulation rate in response to a 10 cmH2O increase in pulmonary artery pressure was also reduced in aged mice by 21.9% compared with young mice (0.32 ± 0.06 vs 0.41 ± 0.04 mg/s, respectively; P < 0.01).
- 4 There was a 62.7% decrease in serum glucocorticoids in aged mice compared with young mice (67.6 ± 26.8 vs 181.3 ± 44.4 nmol/L, respectively; P < 0.01). In vivo administration of dexamethasone (4 mg/kg) for 5 consecutive days to aged mice increased lung AQP‐1 mRNA and protein expression by 2.1 ± 0.1 fold (P < 0.01) and 1.8 ± 0.2 fold (P < 0.01), respectively. Accordingly, osmotically and hydrostatically driven water transport rates increased by 35.6% (P < 0.01) and 31.2% (P < 0.01), respectively.
- 5 The present study provides the first evidence of altered lung water transport associated with downregulation of AQPs in aged lung. Blood glucocorticoid hormone levels are important to maintain normal AQP‐1 expression in the lung microvascular endothelium. Corticosteroid‐induced AQP‐1 upregulation may contribute to the role of corticosteroids in accelerating oedema clearance in aged lung.
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| Keywords: | ageing aquaporin corticosteroid lung water transport oedema |
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