Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice.
Aquaporin (AQP) water channels provide a major pathway for osmotically driven water movement across epithelial and microvascular barriers in the lung. We used mice deficient in each of the three principal lung aquaporins, AQP1, AQP4 and AQP5, to test the hypothesis that aquaporins are important in neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury. Wet-to-dry weight ratios (W/D) in lungs from wild-type mice decreased from 7.9 to 5.7 over the first hour after spontaneous delivery. AQP deletion did not significantly affect W/D at 45 min after birth. Alveolar fluid clearance was measured in living ventilated mice in which 0.5 ml saline containing radiolabelled albumin was instilled into the airspaces. Fluid clearance was 17.4 % in 15 min and inhibited >90 % by amiloride, but clearance was not affected by AQP deletion. W/D was measured in established models of acute lung injury - acid aspiration and thiourea administration. Two hours after intratracheal administration of HCl, W/D increased from 3.7 to 7.5 but was not affected by AQP deletion. Three hours after intraperitoneal infusion of thiourea, W/D increased to 5.5 and marked pleural effusions appeared, but there were no differences in wild-type and AQP knockout mice. Hyperoxic subacute lung injury was induced by 95 % oxygen. Neither mean survival (143 h) nor W/D at 65 h (5.1) were significantly affected by AQP deletion. Despite their role in osmotically driven lung water transport, aquaporins are not required for the physiological clearance of lung water in the neonatal or adult lung, or for the accumulation of extravascular lung water in the injured lung.
Song
Y
Y
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Fukuda
N
N
Bai
C
C
Ma
T
T
Matthay
M A
MA
Verkman
A S
AS
D000143:Acids; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051398:Aquaporin 1; D051401:Aquaporin 4; D051402:Aquaporin 5; D020346:Aquaporins / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism; D007202:Indicators and Reagents; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D010996:Pleural Effusion / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism*; D012121:Respiration, Artificial; D013890:Thiourea; D014882:Water-Electrolyte Balance / Q000502:physiology
D000143:Acids; C496021:Aqp1 protein, mouse; C496031:Aqp4 protein, mouse; C496038:Aqp5 protein, mouse; D051401:Aquaporin 4; D051402:Aquaporin 5; D020346:Aquaporins; D007202:Indicators and Reagents; D008565:Membrane Proteins; D051398:Aquaporin 1; D013890:Thiourea