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Pleiotropic effects of simvastatin in physically trained ovariectomized rats


This study tests the hypothesis that simvastatin treatment can induce cardiovascular, autonomic and membrane lipoperoxidation improvement, which may be further exarcebated when applied in physically trained ovariectomized rats. Ovariectomized rats were divided in groups (n=8): sedentary, sedentary+simvastatin and trained+simvastatin. Exercise training was performed on treadmill for 8 weeks and simvastatin treatment (5mg/kg) was performed in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated by lipoperoxidation in the heart and liver by chemiluminescence method. Simvastatin treated groups presented reduced body weight and mean BP (trained+simvastatin: 99±2 and sedentary+simvastatin: 107±2 vs. sedentary: 122±1 mmHg) as compared to sedentary group. Furthermore, the trained group showed lower BP and heart rate in relation to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin groups. Vagal effect was increased in trained+simvastatin group and sympathetic effect was decreased in sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (H21%) and trained+simvastatin groups (H57%) in relation to sedentary group. Correlation analysis involving all studied animals demonstrated that cardiac lipoperoxidation was negatively related with vagal effect (r=-0.7) and positively correlated with sympathetic effect (r=0.7). In conclusion, improvement on cardiovascular autonomic control associated with a reduction on lipoperoxidation in simvastatin treatment was exacerbated in trained ovariectomized rats, suggesting a positive role of these approaches in the management of dysfunctions associated with ovarian hormones deprivation. (AU)

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