Clinical Interventions in Aging (Mar 2016)
Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress
Abstract
Jacqueline Freire Machi,1,2 Danielle da Silva Dias,3 Sarah Cristina Freitas,3 Oscar Albuquerque de Moraes,1 Maikon Barbosa da Silva,1 Paula Lázara Cruz,1 Cristiano Mostarda,4 Vera M C Salemi,1 Mariana Morris,2 Kátia De Angelis,3 Maria-Cláudia Irigoyen1 1Hypertension Unit, Heart Institute (InCor), School of Medicine, University of Sao Paulo, São Paulo, Brazil; 2Institute of Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; 3Laboratory of Translational Physiology, Universidade Nove de Julho (UNINOVE), São Paulo, 4Health Adult and Child, Federal University of Maranhao (UFMA), São Luiz, Maranhão, Brazil Objective: The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods: Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results: Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress. Keywords: autonomic nervous system, aging, aerobic exercise, female rats
