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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Propranolol treatment lowers blood pressure, reduces vascular inflammatory markers and improves endothelial function in obese mice

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Franco, Nathalia da Silva ; Lubaczeuski, Camila ; Guizoni, Daniele M. ; Victorio, Jamaira A. ; Santos-Silva, Junia C. ; Brum, Patricia C. ; Carneiro, Everardo M. ; Davel, Ana P.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: PHARMACOLOGICAL RESEARCH; v. 122, p. 35-45, AUG 2017.
Citações Web of Science: 8

Obesity-associated hypertension is accompanied by a number of cardiovascular risk factors including vascular insulin resistance (IR) and higher sympathetic nervous activity. Therefore, autonomic blockade was demonstrated to reverse hypertension, endothelial dysfunction and IR in obese individuals. We hypothesized that beta-AR blockade with propranolol would restore endothelial function and vascular insulin signaling in obesity, associated with an anti-inflammatory effect. Body weight, systolic blood pressure (SBP), plasma biochemical parameters and aortic endothelial function were analyzed in mice fed standard diet (control group) or a high fat diet (HFD) that were treated with vehicle (water) or propranolol (10 mg/kg/day) for 8 weeks. Propranolol treatment did not modify obesogenic effect of HFD feeding. However, propranolol was effective in preventing the rise in SBP, the hyperinsulinemia and the impaired endothelium-dependent relaxation to acetylcholine and to insulin in obese mice. Protective effect of propranolol administration in endothelial function was associated with increased nitric oxide (NO) production and phosphorylation of Akt (Ser473) and eNOS (Ser1177), but with reduced phosphoIRS-1(Ser307) and phospho-ERK1/2 (Thr202/Tyr204). In addition, (beta-blocker propranolol prevented the NF-kappa B nuclear translocation and the increase in phospho-I kappa B-alpha (Ser32) and in interleukin(IL)-6 expression in aorta of obese mice, without significant changes in either aortic reactive oxygen species production or in circulating IL-6 and TNF-alpha levels. In beta(2)-AR knockout mice, despite increasing body weight and visceral fat, HFD did not increase SBP and showed a partial improvement of endothelial function, revealing a role of (beta(2)-AR in cardiovascular effects of obesity. In conclusion, our results suggest that beta-AR blockade with propranolol is effective to prevent the endothelial dysfunction, vascular IR and pro-inflammatory state displayed in HFD-induced obesity, independent of changes in body weight. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 15/00074-0 - Análise molecular e funcional dos efeitos do antagonismo dos receptores beta-adrenérgicos nas alterações vasculares de camundongos obesos
Beneficiário:Nathalia Santos da Silva
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 14/07947-6 - Possível interação entre estimulação beta-adrenérgica e ativação do receptor de mineralocorticóide em células endoteliais, musculares lisas e do tecido adiposo perivascular
Beneficiário:Ana Paula Couto Davel
Linha de fomento: Auxílio à Pesquisa - Regular