Long‐Term Treatment with Atorvastatin Reduces Oxidative Stress in Rostral Ventrolateral Medulla Associated with Sympatho‐Inhibitory Effects in Stroke‐Prone Spontaneously Hypertensive Rats

Abstract

Statins have reported to increase endothelial nitric oxide synthase (eNOS) expression and activity independent of cholesterol-lowering effects. We demonstrated that long-term treatment with atorvastatin had sympatho-inhibitory effects with upregulation of eNOS in the brain in stroke-prone spontaneously hypertensive rats (SHRSP). Furthermore, we also demonstrated that reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of the brain stem, where the vasomotor center is located, was significantly increased in SHRSP and that ROS in the RVLM contribute to sympatho-excitatory effects in SHRSP. The aim of the present study was to determine whether atorvastatin reduces oxidative stress in the RVLM of SHRSP associated with sympatho-inhibitory effects. SHRSP and Wistar-Kyoto (WKY) rats were treated with or without atorvastatin (50mg/kg per day) for 30 days. Systolic blood pressure and heart rate were measured using the tail-cuff method. As the parameter of the sympathetic nerve activity, urinary norepinephrine excretion was measured for 24 hours before and after the treatment. Treatment with atorvastatin significantly decreased blood pressure and urinary norepinephrine excretion in SHRSP, but not in WKY. Thiobarbituric acid-reactive substances (TBARS) levels in the RVLM tissue obtained using the punch-out technique were used as measures of oxidative stress. Treatment with atorvastatin decreased TBARS levels in the RVLM of SHRSP but not in WKY. These results suggest that atorvastatin reduces oxidative stress in the RVLM of SHRSP, which might contribute to the sympatho-inhibitory effects of atorvastatin in SHRSP.