Hirooka Yoshitaka, Kimura Yoshikuni, Nozoe Masatsugu, Sagara Yoji, Ito Koji, Sunagawa Kenji
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hypertens Res. 2006 Jan;29(1):49-56. doi: 10.1291/hypres.29.49.
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.
氨氯地平是一种二氢吡啶类钙通道阻滞剂，广泛用于治疗高血压患者，且在体外对血管具有抗氧化作用。本研究的目的是检验氨氯地平治疗是否能降低易患中风的自发性高血压大鼠（SHRSP）大脑中的氧化应激。动物通过饮用水接受氨氯地平、尼卡地平或肼屈嗪治疗30天。在每次治疗前后测量大脑（皮质、小脑、下丘脑和脑干）中的硫代巴比妥酸反应性物质（TBARS）水平。氨氯地平、尼卡地平及肼屈嗪治疗组的收缩压均降至相似水平。氨氯地平治疗后，SHRSP的尿去甲肾上腺素排泄显著减少，但尼卡地平或肼屈嗪治疗后未减少。SHRSP大脑皮质、小脑、下丘脑和脑干中的TBARS水平显著高于Wistar-Kyoto大鼠（WKY），氨氯地平治疗的SHRSP中TBARS水平降低，但尼卡地平或肼屈嗪治疗的SHRSP中未降低。电子自旋共振光谱显示SHRSP大脑中的活性氧水平升高，氨氯地平治疗可降低该水平。脑池内注入氨氯地平也可降低收缩压、尿去甲肾上腺素排泄及大脑中的TBARS水平。这些结果表明，与WKY大鼠相比，SHRSP大脑中的氧化应激增强。此外，氨氯地平降压治疗可降低所检测的大脑所有区域的氧化应激，降低血压，且不会引起SHRSP交感神经活性反射性增加。
