Reduced lung water transport rate associated with downregulation of aquaporin-1 and aquaporin-5 in aged mice.
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 cmH(2)O 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.
Zhang
Ying-Wei
YW
Membrane Channel Research Laboratory, Northeast Normal University, Changchun, PR China.
Bi
Lin-Tao
LT
Hou
Song-Ping
SP
Zhao
Xue-Liang
XL
Song
Yuan-Lin
YL
Ma
Tong-Hui
TH
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D051402:Aquaporin 5 / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D015633:Extravascular Lung Water / Q000378:metabolism*; D051379:Mice; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism / Q000473:pathology
D051402:Aquaporin 5; D051398:Aquaporin 1