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PLoS One. 2014 Jan 23;9(1):e86447. doi: 10.1371/journal.pone.0086447. eCollection 2014.

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

Author information

  • 1Botucatu Medical School, São Paulo State University, Botucatu, Brazil ; School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
  • 2Botucatu Medical School, São Paulo State University, Botucatu, Brazil.
  • 3School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
  • 4Botucatu Biosciences Institute, São Paulo State University, Botucatu, Brazil.

Abstract

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, Tyr-phosphorylated 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.

PMID:
24466104
[PubMed - indexed for MEDLINE]
PMCID:
PMC3900554
Free PMC Article
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