TY - JOUR
T1 - Regulation of alveolar fluid clearance and ENaC expression in lung by exogenous angiotensin II
AU - Deng, Jia
AU - Wang, Dao xin
AU - Deng, Wang
AU - Li, Chang yi
AU - Tong, Jin
AU - Ma, Hilary
N1 - Funding Information:
We acknowledge the review of the manuscript by Hilary Ma, MD, Department of Medicine, New York University Langone Medical Center, New York, NY, U.S.A. We thank all members of Wang laboratory for invaluable advice and discussions. This study was supported by grants from National Natural Science Foundation of China (Grant no. 30971301 ).
PY - 2012/4/15
Y1 - 2012/4/15
N2 - Angiotensin II (Ang II) has been demonstrated as a pro-inflammatory effect in acute lung injury, but studies of the effect of Ang II on the formation of pulmonary edema and alveolar filling remains unclear. Therefore, in this study the regulation of alveolar fluid clearance (AFC) and the expression of epithelial sodium channel (ENaC) by exogenous Ang II was verified. SD rats were anesthetized and were given Ang II with increasing doses (1, 10 and 100μg/kg per min) via osmotic minipumps, whereas control rats received only saline vehicle. AT 1 receptor antagonist ZD7155 (10mg/kg) and inhibitor of cAMP degeneration rolipram (1mg/kg) were injected intraperitoneally 30min before administration of Ang II. The lungs were isolated for measurement of alveolar fluid clearance. The mRNA and protein expression of ENaC were detected by RT-PCR and Western blot. Exposure to higher doses of Ang II reduced AFC in a dose-dependent manner and resulted in a non-coordinate regulation of α-ENaC vs the regulation of β- and γ-ENaC, however Ang II type 1 (AT1) receptor antagonist ZD7155 prevented the Ang II-induced inhibition of fluid clearance and dysregulation of ENaC expression. In addition, exposure to inhibitor of cAMP degradation rolipram blunted the Ang II-induced inhibition of fluid clearance. These results indicate that through activation of AT 1 receptor, exogenous Ang II promotes pulmonary edema and alveolar filling by inhibition of alveolar fluid clearance via downregulation of cAMP level and dysregulation of ENaC expression.
AB - Angiotensin II (Ang II) has been demonstrated as a pro-inflammatory effect in acute lung injury, but studies of the effect of Ang II on the formation of pulmonary edema and alveolar filling remains unclear. Therefore, in this study the regulation of alveolar fluid clearance (AFC) and the expression of epithelial sodium channel (ENaC) by exogenous Ang II was verified. SD rats were anesthetized and were given Ang II with increasing doses (1, 10 and 100μg/kg per min) via osmotic minipumps, whereas control rats received only saline vehicle. AT 1 receptor antagonist ZD7155 (10mg/kg) and inhibitor of cAMP degeneration rolipram (1mg/kg) were injected intraperitoneally 30min before administration of Ang II. The lungs were isolated for measurement of alveolar fluid clearance. The mRNA and protein expression of ENaC were detected by RT-PCR and Western blot. Exposure to higher doses of Ang II reduced AFC in a dose-dependent manner and resulted in a non-coordinate regulation of α-ENaC vs the regulation of β- and γ-ENaC, however Ang II type 1 (AT1) receptor antagonist ZD7155 prevented the Ang II-induced inhibition of fluid clearance and dysregulation of ENaC expression. In addition, exposure to inhibitor of cAMP degradation rolipram blunted the Ang II-induced inhibition of fluid clearance. These results indicate that through activation of AT 1 receptor, exogenous Ang II promotes pulmonary edema and alveolar filling by inhibition of alveolar fluid clearance via downregulation of cAMP level and dysregulation of ENaC expression.
KW - Alveolar fluid clearance
KW - Angiotensin II
KW - Cyclic adenosine monophosphate
KW - Epithelial sodium channel
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U2 - 10.1016/j.resp.2011.11.009
DO - 10.1016/j.resp.2011.11.009
M3 - Article
C2 - 22138610
AN - SCOPUS:84863240520
SN - 1569-9048
VL - 181
SP - 53
EP - 61
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
IS - 1
ER -