Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

Silva, S. D., Jara, Z. P., Peres, R., Lima, L. S., Scavone, C., Montezano, A. C., Touyz, R. M. , Casarini, D. E. and Michelini, L. C. (2017) Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction. PLoS ONE, 12(12), e0189535. (doi: 10.1371/journal.pone.0189535) (PMID:29232407) (PMCID:PMC5726656)

Abstract

Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1–7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes’ diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes’ diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1–7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Montezano, Dr Augusto and Touyz, Professor Rhian
• Authors: Silva, S. D., Jara, Z. P., Peres, R., Lima, L. S., Scavone, C., Montezano, A. C., Touyz, R. M., Casarini, D. E., and Michelini, L. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in PLoS ONE 12(12):e0189535
• Publisher Policy: Reproduced under a Creative Commons License