Sodium channel but neither Na(+)-H+ nor Na-glucose symport inhibitors slow neonatal lung water clearance.
Normal clearance of alveolar liquid following birth requires active Na transport; however, the contribution of Na channels, Na-H antiports, and Na-glucose symports is unknown. We demonstrated that intraalveolar instillation of amiloride (n = 6) or the more specific Na channel blockers benzamil (n = 13) or phenamil (n = 12) before the first breath impaired lung water clearance relative to control newborns (n = 34). Benzamil and phenamil were more potent than amiloride (P less than 0.05). Neither the Na-H antiport inhibitor dimethyl amiloride (n = 7) nor the Na-glucose symport inhibitor phloridzin (n = 7) impaired lung water clearance. Ion substitution experiments with fetal rat type II alveolar epithelia demonstrated that more than 95% of their resting or terbutaline-stimulated short circuit current (Isc) depended upon Na bathing their apical membrane. Isc was decreased by amiloride (IC50 of amiloride-sensitive Isc = 0.3 x 10(-6) M) and benzamil (IC50 of benzamil-sensitive Isc = 0.3 x 10(-7) M) but was unaffected by dimethyl amiloride (10(-4) M). We conclude that in vivo postnatal clearance of fetal lung liquid can be impaired by Na channel blockers and is unaffected by blockers of Na-H antiports and Na-glucose symports. Na transport in fetal type II cells has high affinity for amiloride, and these cells likely contribute to normal neonatal lung liquid clearance.
O'Brodovich
H
H
Department of Paediatrics, University of Toronto, Ontario, Canada.
Hannam
V
V
Rafii
B
B
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001834:Body Water / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004560:Electricity; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D009004:Monosaccharide Transport Proteins; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; C013407:benzamil; C047088:phenylamil; D000584:Amiloride; D010695:Phlorhizin