AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity

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Oliveira-Junior, Silvio A. [UNESP]
Martinez, Paula F. [UNESP]
Guizoni, Danielle M. [UNESP]
Campos, Dijon H. S. [UNESP]
Fernandes, Tiago
Oliveira, Edilamar M.
Okoshi, Marina P. [UNESP]
Okoshi, Katashi [UNESP]
Padovani, Carlos R. [UNESP]
Cicogna, Antonio C. [UNESP]
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Background: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. Material and Methods: Wistar-Kyoto (n = 40) rats were subjected to control (C; 3.2 kcal/g) and hypercaloric diets (OB; 4.6 kcal/g) for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day) for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE), and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP), echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2), c-Jun amino-terminal kinases (JNK), insulin receptor subunit β (βIR), and phosphatidylinositol 3-kinase (PI3K) by Western Blot. Results: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyrphosphorylated βIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-βRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. Conclusion: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes. © 2014 Oliveira-Junior et al.
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PLoS ONE, v. 9, n. 1, 2014.