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Renin Inhibition Attenuates Ang II Induced Oxidative Stress and Remodeling in the Pancreas of the Ren2 Rat (tg (mREN2)27)
Author(s) -
Habibi Javad,
Hayden Melvin R,
DeMarco Vincent G,
WhaleyConnell Adam,
Schneider Rebecca I,
Ferrario Carlos M,
Sowers James R
Publication year - 2008
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.22.1_supplement.758.12
Subject(s) - aliskiren , medicine , endocrinology , nitrotyrosine , oxidative stress , insulin resistance , renin–angiotensin system , renin inhibitor , chemistry , insulin , nitric oxide , blood pressure , nitric oxide synthase
The Ren2 rat expresses the mouse renin gene in numerous extra‐renal sites leading to higher tissue Ang II, oxidative stress, insulin resistance, hypertension, and tissue remodeling. Recently, we showed reversal of oxidative stress, myocardial, renal, and vascular remodeling, and skeletal muscle insulin resistance in the Ren2 after treatment with an AT1R blocker or antioxidant. Here we test whether renin inhibition reverses oxidative stress and remodeling in the pancreas of Ren2. Pancreas was harvested from 9 week old male Ren2 and SD rats following 21 day treatment with 50mg/kg/day aliskiren or placebo. Paraffin sections were incubated with primary antibodies to the NADPH oxidase subunits, NOX2 and Rac1, 3‐nitrotyrosine, complex IV subunit I (mitochondrial marker), and secondary anybodies. Fluorescence of laser confocal images was quantified. VVG stained sections were evaluated for periarterial fibrosis. Signal intensities of Rac1 and 3‐nitrotyrosine, but not NOX2, were elevated in both islets and parenchyma of control Ren2 and aliskiren blunted these changes. Arterial fibrosis found in untreated Ren2 pancreas was prevented by aliskiren. Mitochondrial number, which was higher in control Ren2 pancreas, was lowered by aliskiren. The Ren2 pancreas exhibits oxidative stress and remodeling which are reversed by treatment with aliskiren. Supported by NIH R01‐HL‐63904 and VA Merit (JRS).