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Angiotensin Receptor Blockade Reduces Oxidative Stress while Improving Redox Signaling and Mitochondrial Function in the Heart of Diet‐induced Obese Insulin Resistant Rats
Author(s) -
VazquezMedina Jose Pablo,
Popovich Irina,
Thorwald Max A,
Rodriguez Ruben,
Viscarra Jose A,
Lam Lisa,
PetiPeterd Janos,
Nakano Daisuke,
Nishiyama Akira,
Ortiz Rudy M
Publication year - 2013
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.27.1_supplement.918.3
Subject(s) - oxidative stress , nox4 , medicine , angiotensin ii receptor type 1 , endocrinology , nadph oxidase , angiotensin ii , olmesartan , mitochondrion , chemistry , metabolic syndrome , mitochondrial ros , receptor , diabetes mellitus , biochemistry , blood pressure
The contributions of angiotensin receptor type 1 (AT1) activation to NADPH oxidase (Nox)‐derived oxidative stress during hypertension and diabetes are well established. The role of AT1 in modulating redox signaling, mitochondrial function and oxidative stress in the heart during metabolic syndrome, however, remains elusive. To test the hypothesis that AT1 activation increases oxidative stress while impairing mitochondrial function and redox signaling in the heart during metabolic syndrome, diet‐induced obese, insulin resistant (OLETF) rats were treated with the AT1 blocker (ARB) Olmesartan for 6 weeks. Cardiac Nox2 expression increased 40% in OLETF compared to age‐matched lean (LETO) rats while expression of the H 2 O 2 ‐producing Nox4 increased 40%. ARB treatment prevented the increase in Nox2 without altering Nox4. ARB treatment also normalized increased protein and lipid oxidation and increased the redox‐sensitive transcription factor Nrf2 30%, and antioxidant enzymes by 50–70%. Mitochondrial aconitase activity increased 60% in OLETF compared to LETO whereas succinate decreased 35%; ARB treatment normalized both. These data demonstrate that AT1 activation contributes to increased Nox2‐derived oxidative stress and to impaired redox signaling and mitochondrial activity, and suggests that, besides its anti‐hypertensive effects, ARB treatment may improve myocardial function during metabolic syndrome.