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Original Article

^a From the Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143
^b From the Department of Physiology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143
Cardiovascular Research Institute, 1246 Health Sciences East Tower, Box 0521, University of California, San Francisco, San Francisco, CA 94143-0521.415-665-3847

verkman{at}itsa.ucsf.edu

The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (J_v) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. J_v in wild-type mice varied linearly with osmotic gradient size (4.4 x 10^–5 cm³ s^–1 mOsm^–1) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H₂O outflow pressure, the filtration coefficient was 4.7 cm³ s^–1 mOsm^–1 and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. J_v were (cm³ s^–1 mOsm^–1 x 10^–5, SEM, n = 7–12 mice): 3.8 ± 0.4 (wild type), 0.35 ± 0.02 (AQP1 null), 3.7 ± 0.4 (AQP4 null), and 0.25 ± 0.01 (AQP1/AQP4 null). The significant reduction in P_f in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 ± 0.2-fold (SEM, five mice) reduced P_f in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport.

Key Words: water permeability • airways • transgenic mouse • membrane transport • aquaporin-1

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This article has been cited by other articles:

				Y. Song, S. Jayaraman, B. Yang, M. A. Matthay, and A.S. Verkman Role of Aquaporin Water Channels in Airway Fluid Transport, Humidification, and Surface Liquid Hydration J. Gen. Physiol., June 1, 2001; 117(6): 573 - 582. [Abstract] [Full Text] [PDF]

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