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Sequential effects of the aerobic training in modulating the activity of renin angiotensin system in plasma and tissue

Grant number: 11/15681-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2011
Effective date (End): April 30, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Lisete Compagno Michelini
Grantee:Sebastião Donato Silva Júnior
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

An imbalance between the 2 axes of the renin-angiotensin system (RAS: ACE-Ang II-AT1 receptor and ACE2-Ang (1-7)-Mas receptor) favoring the vasoconstrictor axis is closely related to the development/maintenance of hypertension. It also determined structural and functional changes in major organs such as the kidney and heart. Since previous observations from our laboratory showed that low intensity aerobic training (T) reduces RAS activity in the brain and peripheral vessels, contributing to blood pressure (BP) fall, we aimed now to evaluate the sequential effects of T on the expression of the different RAS components in heart, kidney and plasma and on the balance between vasoconstrictor and vasodilator axes in spontaneous hypertensive rats (SHR) and their normotensive controls (WKY). WKY and SHR will be submitted to low-intensity aerobic training (treadmill: 50-60% of maximum exercise capacity, 1 h/day, 5 days/week) or sedentary (S) protocols for 8 weeks. Baseline BP and heart rate will be measured at weeks zero (S0), one (T1), two (T2), four (T4) and eight (T8 and S8). After functional data acquisition 2 ml of blood will be taken (for plasma measurements), and rats will be deeply anesthetized for transcardiac perfusion (saline buffer) and heart & Kidney removal. Tissues and plasma will be stored (-80oC) until Ang I, Ang II and Ang (1-7) extraction and processing by High Performance Liquid Chromatography (HPLC). Tissues will also be used for angiotensinogen expression and identification of ACE isoforms (Western Blot), as well as for enzymatic activity of ACE (fluorimetry). Results will offer the opportunity to evaluate and compare in different tissues and plasma the effects of aerobic training, associated or not with hypertension, on the balance between the ACE-Ang II-AT1 and ACE2-Ang (1-7)-Mas receptor axes, as well as to correlate these changes with cardiovascular function in trained and sedentary SHR and WKY.

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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)
SILVA, JR., SEBASTIAO D.; ZAMPIERI, THAIS T.; RUGGERI, ADRIANA; CERONI, ALEXANDRE; ARAGAO, DANIELLE S.; FERNANDES, FERNANDA B.; CASARINI, DULCE E.; MICHELINI, LISETE C.. Downregulation of the Vascular Renin-Angiotensin System by Aerobic Training - Focus on the Balance Between Vasoconstrictor and Vasodilator Axes. CIRCULATION JOURNAL, v. 79, n. 6, p. 1372-1380, . (11/15681-8, 10/51904-9)
SILVA JUNIOR, SEBASTIAO DONATO; JARA, ZAIRA; MOREIRA, ROSELI; CASARINI, DULCE; MICHELINI, LISETE. Time-dependent effects of training on cardiac renin angiotensin system (RAS): Protection against oxidative stress, inflammation and pathological cardiac remodeling.. FASEB JOURNAL, v. 31, p. 2-pg., . (11/15681-8)
SILVA, JR., SEBASTIAO D.; JARA, ZAIRA P.; PERES, ROSELI; LIMA, LARISSA S.; SCAVONE, CRISTOFORO; MONTEZANO, AUGUSTO C.; TOUYZ, RHIAN M.; CASARINI, DULCE E.; MICHELINI, LISETE C.. Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction. PLoS One, v. 12, n. 12, . (11/15681-8, 10/51904-9, 11/51410-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA JÚNIOR, Sebastião Donato. Sequential effects of aerobic training on the plasma and cardiac renin angiotensin system in SHR. Analysis of oxidative stress, inflammatory profile and cardiac remodeling.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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