Amlodipine-Induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats
Amlodipine-Induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats
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DOI：
10.1291/hypres.29.49
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Sunagawa, K
中科院分区：
文献类型：
--
作者：
Hirooka, Y;Kimura, Y;Sunagawa, K
氨氯地平是一种二氢吡啶类钙通道阻滞剂，广泛用于高血压患者的治疗，在体外对血管具有抗氧化作用。本研究的目的是检查氨氯地平治疗是否可以减少易发生中风的自发性高血压大鼠（SHRSP）大脑中的氧化应激。这些动物在饮用水中接受氨氯地平、尼卡地平或肼苯达嗪 30 天。每次治疗前后测量大脑（皮质、小脑、下丘脑和脑干）中硫代巴比妥酸反应物质（TBARS）的水平。氨氯地平、尼卡地平和肼屈嗪治疗组的收缩压降低至相似水平。氨氯地平治疗后，SHRSP 的尿去甲肾上腺素排泄量显着减少，但尼卡地平或肼屈嗪治疗后却没有显着减少。 SHRSP 中皮质、小脑、下丘脑和脑干中的 TBARS 水平显着高于 Wistar-Kyoto 大鼠 (WKY)，并且在接受氨氯地平治疗的 SHRSP 中降低，但在接受尼卡地平或肼屈嗪治疗的 SHRSP 中则没有降低。电子自旋共振光谱显示 SHRSP 大脑中活性氧水平升高，而氨氯地平治疗后活性氧水平降低。脑池内输注氨氯地平还可以降低收缩压、尿去甲肾上腺素排泄量以及大脑中 TBARS 的水平。这些结果表明，与 WKY 大鼠相比，SHRSP 大鼠大脑中的氧化应激增强。此外，氨氯地平抗高血压治疗可减少所检查的大脑所有区域的氧化应激，并降低血压，而 SHRSP 的交感神经活动没有反射性增加。
Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.