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Montes Claros, Brazil

Santos C.F.F.,Federal University of Minas Gerais | Santos S.H.S.,Federal University of Minas Gerais | Santos S.H.S.,Laboratory of Health Science | Ferreira A.V.M.,Federal University of Minas Gerais | And 3 more authors.
Peptides | Year: 2013

The β-adrenergic blockers and antagonists of the renin-angiotensin system (RAS) are among the drugs that present better results in the control of cardio-metabolic diseases. The aim of the present study was to evaluate the effect of the association of the β-blocker, atenolol, and an oral formulation of Ang-(1-7) on lipid metabolism in spontaneously hypertensive rats (SHR). The main results showed that SHR treated with oral formulation of Ang-(1-7) in combination to atenolol have an improvement of lipid metabolism with a reduction of total plasma cholesterol, improvement of oral fat load tolerance and an increase in the lipolytic response stimulated by the β-adrenergic agonist, isoproterenol, without modification of resting glucose or insulin sensitivity in adipocytes. In conclusion, we showed that administration of an Ang-(1-7) oral formulation in association with a β-blocker induces beneficial effects on dyslipidemia treatment associated with hypertension. © 2013 Elsevier Inc. All rights reserved.


Bilman V.,Federal University of Minas Gerais | Mares-Guia L.,Federal University of Minas Gerais | Nadu A.P.,Federal University of Minas Gerais | Bader M.,Max Delbruck Center for Molecular Medicine | And 4 more authors.
Peptides | Year: 2012

The renin-angiotensin (Ang) system (RAS) plays an important role in the control of glucose metabolism and glycemia. Several studies demonstrated that the effects of angiotensin-(1-7) are mainly opposite to the actions of biological angiotensin II. Recent studies have demonstrated that rats with increased circulating angiotensin-(1-7), acting through the G protein coupled receptor Mas, have enhanced glucose tolerance and insulin sensitivity, presenting improved metabolic parameters. However, there is no data regarding the role of angiotensin-(1-7)-Mas axis in hepatic glycemic metabolism. In the present study, the gluconeogenesis and glycogenolysis was investigated in Sprague-Dawley (SD) and in TGR(A1-7)3292 (TGR) rats which present approximately twofold increase in plasma Ang-(1-7) levels compared to SD. The pyruvate administration in fasted rats showed a decreased synthesis of glucose in TGR compared to the SD rats, pointing to a downregulation of gluconeogenesis. Supporting this data, the mRNA evaluation of gluconeogenic enzymes showed a significant reduction in phosphoenolpyruvate carboxykinase reinforced by a significantly diminished expression of hepatocyte nuclear factor 4α (HNF-4α), responsible for the regulation of gluconeogenic enzymes. In conclusion our data show that the improved glucose metabolism induced by Ang-(1-7) could be due, at least in part, to a downregulation of hepatic gluconeogenesis. © 2012 Elsevier Inc.


Santos S.H.S.,Federal University of Minas Gerais | Santos S.H.S.,Laboratory of Health Science | Simoes e Silva A.C.,Federal University of Minas Gerais
Current Clinical Pharmacology | Year: 2014

The Renin-Angiotensin System (RAS) is recognized as the main biological system involved in cardiovascular and hydroelectrolyte homeostasis. It is well established in literature that RAS blockers retard the progression of renal failure in type 1 [angiotensin converting enzyme (ACE) inhibitors] and in type 2 [angiotensin type 1 receptor (AT1) antagonists] diabetes mellitus and in non-diabetic chronic kidney diseases. More recently, it was shown that newer therapeutic agents, the renin inhibitors, also exert renoprotective actions. Obesity is recognized as a proinflammatory state often associated with kidney diseases. Recent publications have associated the RAS axis imbalance leading to a predominance of Angiotensin II effects with changes in adipokine levels and actions. In this context, the aim of the current review is to present current evidence on the potential role of RAS blockers in modulating the interaction between adipokines and obesity-related renal disorders. © 2014 Bentham Science Publishers.


Santos S.H.S.,Federal University of Minas Gerais | Santos S.H.S.,Laboratory of Health Science | Fernandes L.R.,Biological science Institute | Pereira C.S.,Laboratory of Health Science | And 6 more authors.
Regulatory Peptides | Year: 2012

Introduction: The aim of the present study was to evaluate the effect of a transgenic-induced chronic increase of Ang-(1-7) on the expression of inflammatory markers in adipose tissue and the metabolic profile in rats treated with high-fat diet. Research design and methods: Transgenic rats expressing an Ang-(1-7)-producing fusion protein (TGR L-3292) and Sprague Dawley (SD) control rats 4. weeks old were treated for 8. weeks with a high-fat diet. Food intake and body weight were measured once a week. Glucose-tolerance and insulin sensitivity tests were performed one week before the sacrifice. At the end of the experiment plasma lipid concentrations were measured in TGR and SD rats. Adipose tissue were weighted and corrected by the body weight. Proinflammatory markers in adipose tissue were analyzed using Western-blotting, real time-PCR and immunohistochemistry. Results: High-fat diet TGR rats presented increased HDL cholesterol levels and decreased abdominal fat mass, without changes in food intake. In addition, rats with increased Ang-(1-7) levels had lower body weight. Molecular analysis revealed decreased IL-1β and COX-2 in adipose tissue. Conclusions: Taken together, these results show that chronic high circulating angiotensin-(1-7) levels protect against metabolic stress induced by a high-fat diet decreasing the proinflammatory profile of adipose tissue. © 2012 Elsevier B.V.

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