title: Regulation of alveolar fluid clearance and ENaC expression in lung by exogenous angiotensin II.
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 100 μg/kg per min) via osmotic minipumps, whereas control rats received only saline vehicle. AT1 receptor antagonist ZD7155 (10 mg/kg) and inhibitor of cAMP degeneration rolipram (1 mg/kg) were injected intraperitoneally 30 min 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.
authors.affiliation: Department of Respiratory Medicine, Second Affiliated of Chongqing Medical University, Chongqing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.forename: Dao-Xin
authors.initials: DX
authors.lastname: Wang
authors.forename: Wang
authors.initials: W
authors.lastname: Deng
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Tong
authors.forename: Hilary
authors.initials: H
authors.lastname: Ma
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D015633:Extravascular Lung Water / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects*; D011654:Pulmonary Edema / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D020889:Rolipram / Q000494:pharmacology; D014882:Water-Electrolyte Balance
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000242:Cyclic AMP; D020889:Rolipram