Mechanisms and sequelae of increased alveolar fluid clearance in hyperoxic rats.
We instilled 4 ml isotonic fluid containing trace amounts of fluorescently labeled dextran (molecular mass 150 kDa) in the lungs of rats exposed to either 85% O(2) for 7 days or to 85% O(2) for 7 days and 100% O(2) for 3 days. We withdrew the fluid every hour for a 3-h period and calculated alveolar fluid clearance (AFC) from changes in dextran concentration. Postinstillation (3 h), AFC values in the control and the two hyperoxic groups were 51 +/- 1, 63 +/- 2, and 62 +/- 3 (SE), respectively (%instilled volume; n > or = 5; P < 0.05). Addition of either 1 mM amiloride or N-ethyl-N-isopropyl amiloride (EIPA) in the instillate decreased the AFC values in all groups 3 h later to approximately 30% of instilled volume. Instillation of phenamil, an irreversible blocker of epithelial Na+ channels into the lungs of rats exposed to 85% O(2) for 7 days and 100% O(2) for 2 days, resulted in a significant increase of their extravascular lung fluid volumes 24 h later. These results demonstrate the existence of EIPA-inhibitable Na+ channels in alveolar epithelial cells in vivo and indicate that an increase in Na+ transport plays an important role in limiting the amount of alveolar edema in O(2)-damaged lungs.
Yue
G
G
Department of Anesthesiology, University of Alabama at Birmingham, 35233, USA.
Matalon
S
S
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003911:Dextrans; D018496:Hyperoxia / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D014882:Water-Electrolyte Balance
D003911:Dextrans; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; C039614:ethylisopropylamiloride