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

Autor(es)

Silva, Jr., Sebastiao D. ^{[1, 2]} ; Jara, Zaira P. ^[3] ; Peres, Roseli ^[3] ; Lima, Larissa S. ^[4] ; Scavone, Cristoforo ^[4] ; Montezano, Augusto C. ^[1] ; Touyz, Rhian M. ^[1] ; Casarini, Dulce E. ^[3] ; Michelini, Lisete C. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF GCRC, Glasgow, Lanark - Scotland

^[2] Univ Sao Paulo, Dept Physiol & Biophys, Biomed Sci Inst, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Med, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Dept Pharmacol, Biomed Sci Inst, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 12, n. 12 DEC 12 2017.
• Citações Web of Science: 9

Resumo

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-18, associated with cardiomyocytes' diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T-1 vs T-4 in WKY-T), normalized oxidative stress (T-2), augmented antioxidant defense (T-4) and reduced both collagen deposition and inflammatory profile (T-8), without changing cardiomyocytes' diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T-2-T-4) and reduced BP (T-8). 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. (AU)

• Processo FAPESP: 11/15681-8 - Efeitos sequências do treinamento aeróbio na modulação da atividade do sistema renina-angiotensina plasmático e tecidual
• Beneficiário: Sebastião Donato Silva Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/51904-9 - Sistema renina angiotensina e calicreina cininas na hipertensão, obesidade, diabetes, desnutrição e sepses: mecanismos moleculares, celulares e fisiopatológicos
• Beneficiário: Dulce Elena Casarini
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/51410-9 - Amelioration of the autonomic imbalances of old age with exercise: exploring the molecular and physiological mechanisms
• Beneficiário: Lisete Compagno Michelini
• Modalidade de apoio: Auxílio à Pesquisa - Temático