Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

• Published in: American journal of physiology. Heart and circulatory physiology 2015-10, Vol.309 (7), p.H1115-H1122
• Main Authors: Masson, Gustavo Santos, Nair, Anand R, Silva Soares, Pedro Paulo, Michelini, Lisete Compagno, Francis, Joseph
• Format: Article
• Language: English
• Subjects: Animals; Arterial Pressure; Autonomic Nervous System - physiology; Autonomic Nervous System - physiopathology; Baroreflex - physiology; Cardiovascular system; Cytokines; Cytokines - immunology; Cytokines - metabolism; Exercise; Heart Rate - physiology; HMGB1 Protein - metabolism; I-kappa B Proteins - metabolism; Inflammation; Interleukin-6 - immunology; Interleukin-6 - metabolism; Intubation; Microglia - metabolism; Microglia - physiology; NF-KappaB Inhibitor alpha; Paraventricular Hypothalamic Nucleus - immunology; Paraventricular Hypothalamic Nucleus - metabolism; Phosphorylation; Physical Conditioning, Animal; Protein expression; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, CXCR4 - immunology; Receptors, CXCR4 - metabolism; Rodents; Signal Transduction; Sympathetic Nervous System - physiology; Sympathetic Nervous System - physiopathology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Vagus Nerve - physiology; Vagus Nerve - physiopathology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00349.2015

Exercise training (ExT) is recommended to treat hypertension along with pharmaceutical antihypertensive therapies. Effects of ExT in hypothalamic content of high mobility box 1 (HMGB1) and microglial activation remain unknown. We examined whether ExT would decrease autonomic and cardiovascular abnormalities in spontaneously hypertensive rats (SHR), and whether these effects were associated with decreased HMGB1 content, microglial activation, and inflammation in the hypothalamic paraventricular nucleus (PVN). Normotensive Wistar-Kyoto (WKY) rats and SHR underwent moderate-intensity ExT for 2 wk. After ExT, cardiovascular (heart rate and arterial pressure) and autonomic parameters (arterial pressure and heart rate variability, peripheral sympathetic activity, cardiac vagal activity, and baroreflex function) were measured in conscious and freely-moving rats through chronic arterial and venous catheterization. Cerebrospinal fluid, plasma, and brain were collected for molecular and immunohistochemistry analyses of the PVN. In addition to reduced heart rate variability, decreased vagal cardiac activity and increased mean arterial pressure, heart rate, arterial pressure variability, cardiac, and vasomotor sympathetic activity, SHR had higher HMGB1 protein expression, IκB-α phosphorylation, TNF-α and IL-6 protein expression, and microglia activation in the PVN. These changes were accompanied by higher plasma and cerebrospinal fluid levels of HMGB1. The ExT + SHR group had decreased expression of HMGB1, CXCR4, SDF-1, and phosphorylation of p42/44 and IκB-α. ExT reduced microglial activation and proinflammatory cytokines content in the PVN, and improved autonomic control as well. Data suggest that training-induced downregulation of activated HMGB1/CXCR4/microglia/proinflammatory cytokines axis in the PVN of SHR is a prompt neural adaptation to counterbalance the deleterious effects of inflammation on autonomic control.