Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice

The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascu lar endothelia and aquaporin-4 (AQP4) in airway epithelia To test whether t hese water channels facilitate fluid movement between airspace, interstitia l, and capillary compartments, we measured passive and active fluid transpo rt in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeab ility (PF) was measured in isolated perfused lungs by a pleural surface flu orescence method. P-f was remarkably reduced in AQP1 (-/-) mice (measured i n cm/s x 0.001, SE, n = 5-10: 17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP1 [+/-]; 1.7 /- 0.3 AQP1 [-/-]; 12 +/- 1 AQP4 [-/-]). Microvascular endothelial water pe rmeability, measured by a related pleural surface fluorescence method in wh ich the airspace was filled with inert perfluorocarbon, was reduced more th an 10-fold in AQP1 (-/-) vs. (+/+) mice. Hydrostatically induced lung inter stitial and alveolar edema was measured by a gravimetric method and by dire ct measurement of extravascular lung water. Both approaches indicated a mor e than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to IO-cm H2O increase in pulmonary artery pressur e for five minutes. Active, near-isosmolar alveolar fluid absorption a,) wa s measured in in situ perfused lungs using I-125-albumin as an airspace flu id volume marker. J(v) (measured in percent fluid uptake at 30 min,n = 5) i n (+/+) mice was 6.0 +/- 0.6 (37 degrees C), increased to 16 +/- I by beta- agonists, and inhibited to less than 2.0 by amiloride, ouabain, or cooling to 23 degrees C. J(v) (with isoproterenol) was not affected by aquaporin de letion (18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP1 [-/-]; 16.3 +/- 1.7 AQP4 [-/- ]). These results indicate that osmotically driven water transport across m icrovessels in adult lung occurs by a transcellular route through AQP1 wate r channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport. AQP1 facilitates hydrostati cally driven lung edema but is not required for active near-isosmolar absor ption of alveolar fluid.