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AT1 receptor blocker attenuates mechanical ventilation‐induced atrophy and oxidative stress in the diaphragm muscle (1102.39)
Author(s) -
Kwon OhSung,
Smuder Ashley,
Sollanek Kurt,
Wiggs Michael,
Talbert Erin,
Scott Powers
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1102.39
Subject(s) - losartan , medicine , endocrinology , angiotensin ii , diaphragm (acoustics) , angiotensin ii receptor type 1 , chemistry , mitochondrial ros , oxidative stress , receptor , physics , loudspeaker , acoustics
Background: Mechanical ventilation (MV) is a method of maintaining adequate gas exchange in patients who are unable to sustain adequate alveolar ventilation on their own. Recently, our lab demonstrated that Angiotensin II (Ang II) is a possible mechanism that causes MV‐induced diaphragm muscle atrophy. During MV, elevation of Ang II induces Reactive Oxygen Species (ROS) emission from mitochondria and results in activation of key proteases, calpain and caspase‐3, in the diaphragm. To determine Ang II is a required upstream signal for MV‐induced diaphragm muscle atrophy and contractile dysfunction, we used AT1 receptor blocker (Losartan) and ACE inhibitor (Enalapril), which prevent the elevation of plasma Ang II levels during MV. Methods: Adult female rats were randomly assigned to one of six experimental groups (n =12 each) (1) Spontaneous breathing (SB) with salin, (2) SB with Losartan (LOS), (3) SB with Enalapril (ENA), (4) MV with salin, (5) MV with LOS, (6) MV with ENA. Dependent measures included plasma Ang II levels, diaphragmatic muscle fiber cross‐sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm. Results: ENA attenuates increased circulating Ang II levels during 12 hours prolonged MV but LOS does not. However, only LOS attenuated MV‐induced diaphragm muscle atrophy. As well as, LOS attenuated MV‐induced mitochondrial dysfunction, ROS production, and proteasome activity during. Therefore, Ang II does not appear to be a possible upstream mechanism to prevent MV‐induced diaphragm muscle atrophy. AT1 receptor blocker, losartan has an antioxidant effect and attenuates MV‐induced VIDD. Therefore, the results of our experiments could lead to human clinical trials using losartan as a therapeutic intervention to prevent VIDD.