Kishi Takuya, Hirooka Yoshitaka, Shimokawa Hiroaki, Takeshita Akira, Sunagawa Kenji
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Clin Exp Hypertens. 2008 Jan;30(1):3-11. doi: 10.1080/10641960701813429.
Previously, we demonstrated that atorvastatin has sympatho-inhibitory effects with the upregulation of nitric oxide synthase in the brain in stroke-prone spontaneously hypertensive rats (SHRSP), and that reactive oxygen species in the rostral ventrolateral medulla (RVLM), where the vasomotor center is located, mediate the sympatho-excitatory effect. The aim of the present study was to determine if atorvastatin reduces oxidative stress in the RVLM of SHRSP along with the sympatho-inhibitory effect. SHRSP and Wistar-Kyoto (WKY) rats received standard feed with atorvastatin (50mg/kg per day) or standard feed for 30 days. Systolic blood pressure and heart rate were evaluated using the tail-cuff method. Urinary norepinephrine excretion was measured for 24 hours. After 30 days in SHRSP, blood pressure and urinary norepinephrine excretion were significantly lower in the atorvastatin group than in the control group. Thiobarbituric acid-reactive substance (TBARS) levels in the RVLM tissue obtained using the micropunch technique were used as measures of oxidative stress. Prior to the treatment, TBARS levels in the RVLM of SHRSP were significantly higher than those of WKY. After 30 days, TBARS levels in the RVLM of SHRSP were significantly lower in the atorvastatin group than in the control group. After 30 days in WKY, however, there were no differences in blood pressure, urinary norepinephrine excretion, and TBARS levels between the atorvastatin and control groups. 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.
此前，我们证明阿托伐他汀对易患中风的自发性高血压大鼠（SHRSP）具有交感神经抑制作用，并能上调其大脑中的一氧化氮合酶，且位于血管运动中枢的延髓头端腹外侧区（RVLM）中的活性氧介导了交感神经兴奋作用。本研究的目的是确定阿托伐他汀是否在降低SHRSP的RVLM氧化应激的同时产生交感神经抑制作用。SHRSP和Wistar-Kyoto（WKY）大鼠接受含阿托伐他汀（每天50mg/kg）的标准饲料或标准饲料，持续30天。使用尾套法评估收缩压和心率。测量24小时尿去甲肾上腺素排泄量。30天后，SHRSP中阿托伐他汀组的血压和尿去甲肾上腺素排泄量显著低于对照组。使用微量穿孔技术获得的RVLM组织中的硫代巴比妥酸反应物质（TBARS）水平用作氧化应激的指标。治疗前，SHRSP的RVLM中TBARS水平显著高于WKY。30天后，SHRSP的RVLM中阿托伐他汀组的TBARS水平显著低于对照组。然而，30天后，WKY中阿托伐他汀组和对照组在血压、尿去甲肾上腺素排泄量和TBARS水平上没有差异。这些结果表明，阿托伐他汀可降低SHRSP的RVLM中的氧化应激，这可能有助于阿托伐他汀对SHRSP的交感神经抑制作用。
