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Molecular and functional analysis of beta-adrenoceptors antagonism on the vascular alterations of obese mice

Grant number: 15/00074-0
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2015
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Ana Paula Couto Davel
Grantee:Nathalia Santos da Silva
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Obesity is a worldwide epidemic often associated with type II diabetes (T2DM) and Cardiovascular Diseases (CVD), decreasing quality and life expectancy. Obesity is associated with hyperinsulinemia and Insulin Resistance (IR), as well as with high glucagon secretion and sympathetic nervous system activation. Physiologically, insulin plays a role in vascular homeostasis and stimulates Nitric Oxide (NO) production in the endothelial cells through receptor type tyrosine kinase, which activates phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), stimulating the activity of endothelial NO synthase (eNOS). However, hyperinsulinemia and IR impair the vasodilator action of insulin and contribute to endothelial dysfunction and increased vascular tone. Sympathetic hyperactivity is an important risk factor for CVD and ²-adrenoceptors (²-AR) antagonists are used to treat heart failure and hypertension. Data from our research group has been demonstrated that ²-AR hyperactivation increases the production of Reactive Oxygen Species (ROS) and proinflammatory cytokines in the aorta, which reduces the bioavailability of NO and increases vascular contractile response. In this study we hypothesized that blockade of ²-AR hyperactivation would provide beneficial vascular effects in high fat-induced obese mice diet by improving endothelial function, production of ROS, inflammatory mediators, and signaling of insulin and glucagon. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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. Propranolol treatment lowers blood pressure, reduces vascular inflammatory markers and improves endothelial function in obese mice. PHARMACOLOGICAL RESEARCH, v. 122, p. 35-45, AUG 2017. Web of Science Citations: 8.

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