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.
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.
Authors: H Hager; T H Kwon; A K Vinnikova; S Masilamani; H L Brooks; J Frøkiaer; M A Knepper; S Nielsen Journal: Am J Physiol Renal Physiol Date: 2001-06
Authors: Meshell D Johnson; Hui-Fang Bao; My N Helms; Xi-Juan Chen; Zac Tigue; Lucky Jain; Leland G Dobbs; Douglas C Eaton Journal: Proc Natl Acad Sci U S A Date: 2006-03-20 Impact factor: 11.205
Authors: P M Hassoun; F S Yu; C G Cote; J J Zulueta; R Sawhney; K A Skinner; H B Skinner; D A Parks; J J Lanzillo Journal: Am J Respir Crit Care Med Date: 1998-07 Impact factor: 21.405
Authors: Chhinder P Sodhi; Christine Wohlford-Lenane; Yukihiro Yamaguchi; Thomas Prindle; William B Fulton; Sanxia Wang; Paul B McCray; Mark Chappell; David J Hackam; Hongpeng Jia Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-09-21 Impact factor: 5.464
Authors: Charles D Bengtson; Robert N Montgomery; Usman Nazir; Lewis Satterwhite; Michael D Kim; Nathan C Bahr; Mario Castro; Nathalie Baumlin; Matthias Salathe Journal: Front Med (Lausanne) Date: 2021-02-17