Triiodo-L-thyronine rapidly stimulates alveolar fluid clearance in normal and hyperoxia-injured lungs.
BACKGROUND
Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na, K-ATPase and other ion transport proteins.


OBJECTIVE
In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T(3)).


METHODS
AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time.


RESULTS
Systemic treatment with intraperitoneal injections of T(3) for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T(3)-treated rats had higher Na, K-ATPase hydrolytic activity. T(3) (10(-6) M), but not reverse T(3) (3,3',5' triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T(3) in ex vivo isolated lungs, suggesting a direct effect of T(3) on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T(3) rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury.


CONCLUSIONS
Airspace T(3) rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.
Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Maneesh
M
Bhargava
Marie R
MR
Runyon
Dmitri
D
Smirnov
Jianxun
J
Lei
Thomas J
TJ
Groppoli
Cary N
CN
Mariash
O Douglas
OD
Wangensteen
David H
DH
Ingbar
D000818:Animals; D002478:Cells, Cultured; D007274:Injections, Intraperitoneal; D008297:Male; D011654:Pulmonary Edema / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D000254:Sodium-Potassium-Exchanging ATPase