Time-Dependent Effects of Training on Cardiovascular Control in Spontaneously Hypertensive Rats: Role for Brain Oxidative Stress and Inflammation and Baroreflex Sensitivity

Autor(es)

Masson, Gustavo S. ^[1] ; Costa, Tassia S. R. ^[1] ; Yshii, Lidia ^[2] ; Fernandes, Denise C. ^[3] ; Silva Soares, Pedro Paulo ^[4] ; Laurindo, Francisco R. ^[3] ; Scavone, Cristoforo ^[2] ; Michelini, Lisete C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Heart, Vasc Biol Lab, Sao Paulo - Brazil

^[4] Univ Fed Fluminense, Dept Physiol & Pharmacol, Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 5 MAY 1 2014.
• Citações Web of Science: 39

Resumo

Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-kappa B content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172 +/- 3 mmHg), pressure variability and heart rate (358 +/- 7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47(phox) and reactive oxygen species production, elevated NF-kappa B activity and increased TNF-alpha and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04 +/- 0.31 vs. 2.31 +/- 0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall. (AU)

• Processo FAPESP: 09/54299-1 - Efeitos da remoção seletiva dos barorreceptores arteriais sobre a expressão e funcionalidade de projeções vasopressinergicas e ocitocinérgicas ao bulbo dorsal e ventral sobre o controle autonômico
• Beneficiário: Lisete Compagno Michelini
• Modalidade de apoio: Auxílio à Pesquisa - Regular