• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2020.tde-22012020-113902
Document
Author
Full name
Bruno Vinicius Duarte Marques
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Akamine, Eliana Hiromi (President)
Diniz, Gabriela Placoná
Silva, Cristina Antoniali
Tirapelli, Carlos Renato
Title in Portuguese
Obesidade reduz a participação do receptor AT2 na ação anticontrátil do tecido adiposo perivascular da aorta torácica de camundongos.
Keywords in Portuguese
Obesidade
Sistema renina-angiotensina
Tecido adiposo perivascular
Abstract in Portuguese
A obesidade predispõe a inúmeras doenças que vem causando milhares de mortes por ano, sendo um problema de saúde pública na maior parte do mundo. Disfunção do tecido adiposo está associada ao desenvolvimento dessas doenças. O tecido adiposo perivascular (PVAT) é um depósito que está localizado circundando os vasos sanguíneos e libera diversas moléculas vasodilatadoras e vasoconstritoras, que atuam tanto no músculo liso vascular quanto no endotélio, participando do controle do tônus vascular. Assim, disfunção do PVAT pode levar ao desenvolvimento de doenças vasculares. Vários componentes do sistema renina angiotensina aldosterona (SRAA) estão expressos no PVAT, sendo que estes podem participar do controle do tônus vascular. O objetivo do presente projeto é avaliar o papel dos eixos vasodilatadores do SRAA (angiotensina II/receptor AT2 e enzima conversora de angiotensina 2/angiotensina 1-7/receptor Mas) na ação anticontrátil do PVAT da aorta torácica de camundongos obesos. Camundongos C57Bl/6 de 4 semanas de idade foram submetidos à dieta controle (CTL) ou hiperlipídica (OB) por 16 semanas. No final deste período, foi realizada a caracterização da obesidade e avaliação da reatividade vascular de anéis de aorta torácica sem (PVAT-) e com (PVAT+) PVAT para noradrenalina, incubadas ou não com o antagonista do receptor AT2 (PD123,319), antagonista do receptor Mas (A779) e inibidor da óxido nítrico sintase (L-NAME). Nossos resultados mostram que o efeito anticontrátil do PVAT da aorta torácica está prejudicado em camundongos OB, devido a menor participação do receptor AT2, porém essa disfunção independe de alterações da sinalização do receptor Mas e do óxido nítrico. A expressão proteica dos receptores AT2 foi reduzida na aorta e aumentada no PVAT de camundongos OB. Para confirmar a participação do receptor AT2 no efeito anticontrátil do PVAT da aorta torácica, curvas para noradrenalina foram realizadas em anéis PVAT- e PVAT+ de camundongos nocautes para esse receptor (KO), que foram alimentados com dieta controle (CTL KO) e hiperlipídica (OB KO). Mostramos que o PVAT dos animais CTL KO não possui efeito anticontrátil e que a presença do PVAT aumenta a contração à noradrenalina em camundongos KO. Portanto, nossos resultados mostram que a presença do receptor AT2 é essencial para o efeito anticontrátil do PVAT da aorta.
Title in English
Obesity reduces AT2 receptor participation in anti-contractile effect of mice aortic perivascular adipose tissue.
Keywords in English
Obesity
Perivascular adipose tissue
Renin-angiotensin system
Abstract in English
Obesity predisposes to numerous diseases that have been causing thousands of deaths per year, being a public health problem in most of the world. Adipose tissue dysfunction is associated with the development of these diseases. Perivascular adipose tissue (PVAT) is a deposit that is located around the blood vessels and releases several vasodilator and vasoconstrictor molecules that act on both vascular smooth muscle and endothelium, participating in the control of vascular tone. Thus, PVAT dysfunction can lead to the development of vascular diseases. Several components of the renin angiotensin aldosterone system (RAAS) are expressed in PVAT, which may participate in the control of vascular tone. The aim of the present study is to evaluate the role of the RAAS vasodilator axes (angiotensin II/ AT2 receptor and angiotensin converting enzyme 2/ angiotensin 1-7/ Mas receptor) in the anti-contractile action of PVAT in the thoracic aorta of obese mice. Four-week-old C57Bl/6 mice were submitted to a control (CTL) or high-fat (OB) diet for 16 weeks. At the end of this period, the characterization of obesity and assessment of vascular reactivity of thoracic aorta rings without (PVAT-) and with (PVAT+) PVAT for norepinephrine were performed in the absence and presence of AT2 receptor antagonist (PD123,319), Mas receptor antagonist (A779) and nitric oxide synthase inhibitor (L-NAME). Our results show that the anti-contractile effect of thoracic aortic PVAT is impaired in OB mice due to lower participation of the AT2 receptor, but this dysfunction is independent of changes in Mas receptor signaling and nitric oxide. AT2 receptor protein expression was reduced in the aorta and increased in the PVAT of OB mice. To confirm the participation of the AT2 receptor in the anti-contractile effect of thoracic aortic PVAT, curves for norepinephrine were performed in PVAT- and PVAT+ rings from knockout mice for this receptor (KO), which were fed a control (CTL KO) and high-fat diet (OB KO). We show that the PVAT of CTL KO animals has no anti-contractile effect and that the presence of PVAT increases the norepinephrine contraction in OB KO mice. Therefore, our results show that the presence of the AT2 receptor is essential for the anti-contractile effect of aortic PVAT.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
There are withheld file due to requirements (data publishing, patents or rights).
Release Date
2022-01-21
Publishing Date
2020-02-14
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2020. All rights reserved.