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 (AT(1)) 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 AT(1) 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 AT(1) receptors, which contribute to alveolar filling and pulmonary edema in LPS-induced ALI.