Regulation of alveolar fluid clearance and ENaC expression in lung by exogenous angiotensin II

Jia Deng, Dao xin Wang, Wang Deng, Chang yi Li, Jin Tong, Hilary Ma

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalRespiratory Physiology and Neurobiology
Volume181
Issue number1
DOIs
StatePublished - Apr 15 2012
Externally publishedYes

Keywords

  • Alveolar fluid clearance
  • Angiotensin II
  • Cyclic adenosine monophosphate
  • Epithelial sodium channel

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology
  • Pulmonary and Respiratory Medicine

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