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Effect of renin inhibition on cardiac remodeling in the transgenic, Ren2 rat
Author(s) -
Cooper Shawna,
WhaleyConnell Adam,
Habibi Javad,
Stump Craig,
Hayden Melvin R,
Ferrario Carlos,
Sowers James
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.21.6.lb98
Renin‐angiotensin system (RAS) overactivation contributes to cardiac remodeling and dysfunction. Aliskiren, a non‐peptide renin inhibitor, abrogates RAS overactivation by inhibiting the rate limiting step in Angiotensin‐II formation. This study determined the effects of direct renin inhibition on cardiac remodeling in a rodent model of chronic Ang‐II elevation, the transgenic TG (mRen2) 27 rat. The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, and cardiovascular injury. 6–7 week old, male Ren2 and age‐matched Sprague‐Dawley rats were treated with either aliskiren (Ren2‐A; 50 mg/kg) or placebo (Ren2‐C) for three weeks. Immunohistochemical analyses of NADPH subunits gp91 phox , p22 phox , Rac1, p47, and p67, as well as, 3‐nitrotyrosine, were conducted. Structural changes were assessed with transmission electron microscopy (TEM) and light microscopy. Increases in perivascular and interstitial fibrosis, increased mitochondria, and other ultrastructural changes were apparent in the Ren2‐C with light and TEM (p<0.05); abnormalities which, along with elevated blood pressure, were attenuated in Ren2‐A (p<0.05). Rac1 and p47 were elevated in the Ren2‐C (p<0.05) and decreased in Ren2‐A (p<0.05). Collectively, these data suggest that direct renin inhibition abrogates the deleterious effects of RAS activation of NADPH oxidase/ROS on cardiac remodeling.