Angiotensin-(1-7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats.
Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1-7 [Ang-(1-7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180-200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1-7)-treated normoxia control (N-A), and Ang-(1-7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4) and Nox subunits (p22phox, and p47phox) was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01). Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1-7) treatment. In summary, treatment with Ang-(1-7) reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
W
W
Lu
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
J
J
Kang
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
K
K
Hu
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
S
S
Tang
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
X
X
Zhou
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
S
S
Yu
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
Y
Y
Li
Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, China.
L
L
Xu
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D000860:Hypoxia / Q000150:complications*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000150:complications; D014665:Vasodilator Agents / Q000494:pharmacology*
D016207:Cytokines; D010446:Peptide Fragments; D020011:Protective Agents; D014665:Vasodilator Agents; D008315:Malondialdehyde; D000803:Angiotensin I; C118790:angiotensin I (1-7)