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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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.
Total Authors: 8
Document type: Journal article
Source: PHARMACOLOGICAL RESEARCH; v. 122, p. 35-45, AUG 2017.
Web of Science Citations: 8
Abstract

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)

FAPESP's process: 14/07947-6 - Possible linkage of beta-adrenergic overstimulation to mineralocorticoid receptor activation in endothelial, smooth muscle and adipocyte vascular cells
Grantee:Ana Paula Couto Davel
Support type: Regular Research Grants
FAPESP's process: 15/00074-0 - Molecular and functional analysis of beta-adrenoceptors antagonism on the vascular alterations of obese mice
Grantee:Nathalia Santos da Silva
Support type: Scholarships in Brazil - Master