Role of aquaporins in alveolar fluid clearance in neonatal and adult lung,and in oedema formation following acute lung injury: studies in transgenicaquaporin null mice

1. Aquaporin (AQP) water channels provide a major pathway for osmotically d riven water movement across epithelial and microvascular barriers in the lu ng. We used mice deficient in each of the three principal lung aquaporins, AQP1, AQP4 and AQP5, to test the hypothesis that aquaporins are important i n neonatal lung fluid balance, adult lung fluid clearance and formation of lung oedema after acute lung injury. 2. Wet-to-dry weight ratios (W/D) in lungs from wild-type mice decreased fr om 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. 3. Alveolar fluid clearance was measured in living ventilated mice in which 0.5 ml saline containing radiolabelled albumin was instilled into the airs paces. Fluid clearance was 17.4% in 15 min and inhibited > 90 % by amilorid e, but clearance was not affected by AQP deletion. 4. W/D was measured in established models of acute lung injury - acid aspir ation and thiourea administration. Two hours after intratracheal administra tion of HCl, W/D increased from 3.7 to 7.5 but was not affected by AQP dele tion. Three hours after intraperitoneal infusion of thiourea, W/D increased to 5.5 and marked pleural effusions appeared, but there were no difference s in wild-type and AQP knockout mice. 5. Hyperoxic subacute lung injury was induced by 95% oxygen. Neither mean s urvival (143 h) nor W/D at 65 h (5.1) were significantly affected by AQP de letion. 6. Despite their role in osmotically driven lung water transport, aquaporin s are not required for the physiological clearance of lung water in the neo natal or adult lung, or for the accumulation of extravascular lung water in the injured lung.