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Training-Induced Deactivation of the AT1 Receptor Pathway Drives Autonomic Control and Heart Remodeling During the Transition From the Pre- to Hypertensive Phase in Spontaneously Hypertensive Rats.

Authors
  • da Costa, Tassia Santos Rodrigues1
  • Masson, Gustavo Santos1
  • Eichler, Rosangela Aparecida Dos Santos2
  • Silva, Juliane Cristina de Souza3
  • Lacchini, Silvia3
  • Michelini, Lisete Compagno1
  • 1 Department of Physiology and Biophysics, Biomedical Sciences Institute, University of Sao Paulo.
  • 2 Department of Pharmacology, Biomedical Sciences Institute, University of Sao Paulo.
  • 3 Department of Anatomy, Biomedical Sciences Institute, University of Sao Paulo.
Type
Published Article
Journal
Circulation journal : official journal of the Japanese Circulation Society
Publication Date
Jul 22, 2020
Volume
84
Issue
8
Pages
1294–1303
Identifiers
DOI: 10.1253/circj.CJ-19-1161
PMID: 32522899
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.Methods and Results:Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes' hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT1R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8thweek onwards). Marked AT1R protein content, myocytes's hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension. The close temporal relationship between changes in the LV ACE-Ang II-AT1R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT1R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase.

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