Single dexamethasone injection increases alveolar fluid clearance in adult rats.
OBJECTIVE
Epithelial Na+ channels and Na+/K+-adenosine triphosphatase (ATPase) in alveolar epithelium have a very important role in the absorption of excessive fluid from the alveolar space. We examined whether single dexamethasone injection at therapeutic doses would modulate lung epithelial Na+ channels and Na+/K+-ATPase and increase alveolar fluid clearance in adult rats.


METHODS
Controlled laboratory study.


METHODS
University research laboratory.


METHODS
Adult male Sprague-Dawley rats (n = 138).


METHODS
Rats were intraperitoneally injected with dexamethasone at a dose ranging from 0.02 to 2.0 mg/kg, and allowed free access to food and water.


RESULTS
Alveolar fluid clearance was determined by measuring the increase in albumin concentration in the lung instillate solution. We discovered a significant increase in alveolar fluid clearance at 48 and 72 hrs after dexamethasone treatment. The effect of dexamethasone was dose dependent. In addition, increased alveolar fluid clearance was associated with a faster recover from hypoxemia, which was induced by filling the alveolar space with instillate solution. The dexamethasone-induced increase in alveolar fluid clearance was inhibited by amiloride and ouabain. Quantitative reverse transcriptase-polymerase chain reaction showed that dexamethasone treatment increased lung beta-epithelial Na+ channel mRNA levels. The expression of gamma-epithelial Na+ channel mRNA was also increased slightly. In contrast, alpha-epithelial Na+ channel mRNA levels did not differ from control levels. There was no change in alpha1- or beta1-Na+/K+-ATPase mRNA levels over 72 hrs after dexamethasone treatment. However, we found that lung Na+/K+-ATPase hydrolytic activity, determined by monitoring the ouabain-sensitive ATPase hydrolysis, was increased at 48 and 72 hrs after dexamethasone treatment.


CONCLUSIONS
Single dexamethasone injection at therapeutic doses is capable of modulating lung epithelial Na+ channels and Na+/K+-ATPase and increase alveolar fluid clearance, thereby accelerating recovery from pulmonary edema.
Noda
Masafumi
M
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Suzuki
Satoshi
S
Tsubochi
Hiroyoshi
H
Sugita
Makoto
M
Maeda
Sumiko
S
Kobayashi
Seiichi
S
Kubo
Hiroshi
H
Kondo
Takashi
T
D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D012333:RNA, Messenger; D015222:Sodium Channels; D010042:Ouabain; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase