The effect of endogenous angiotensin II on alveolar fluid clearance in rats with acute lung injury.
BACKGROUND
In acute lung injury (ALI), angiotensin II (Ang II) plays a vital role in the stimulation of pulmonary permeability edema formation through the angiotensin type 1 (AT1) receptor. The effect of Ang II on alveolar fluid clearance (AFC) in ALI remains unknown.


METHODS
Sprague Dawley rats were anesthetized and intratracheally injected with 1 mg⁄kg lipopolysaccharide (LPS), while control rats received saline. The AT1 receptor antagonist ZD7155 was injected intraperitoneally (10 mg⁄kg) 30 min before LPS administration. The lungs were isolated for AFC measurement, and alpha-epithelial sodium channel (ENaC) messenger RNA and protein expression were detected by reverse-transcription polymerase chain reaction and Western blot.


RESULTS
LPS-induced ALI caused an increase in Ang II levels in plasma and lung tissue but a decrease in AFC. The time course of Ang II levels paralleled that of AFC. Pretreatment with ZD7155 prevented ALI-induced reduction of AFC. ZD7155 also reversed the ALI-induced reduction of beta-ENaC and gamma-ENaC levels, and further decreased alpha-ENaC levels.


CONCLUSIONS
These findings suggest that endogenous Ang II inhibits AFC and dysregulates ENaC expression via AT1 receptors, which contribute to alveolar filling and pulmonary edema in LPS-induced ALI.
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jia
J
Deng
Dao-Xin
DX
Wang
Wang
W
Deng
Chang-Yi
CY
Li
Jin
J
Tong
D055371:Acute Lung Injury / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D053503:Epithelial Sodium Channels / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053503:Epithelial Sodium Channels; D008070:Lipopolysaccharides; D009287:Naphthyridines; D012333:RNA, Messenger; C095905:ZD 7155; D000804:Angiotensin II