Amelioration of Hypertensive Heart Failure by Amlodipine May Occur via Antioxidative Effects
Amelioration of Hypertensive Heart Failure by Amlodipine May Occur via Antioxidative Effects
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DOI：
10.1291/hypres.29.719
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发表时间：
2006-09
影响因子：
5.4
通讯作者：
H. Hasegawa;H. Takano;T. Kohro;Kazutaka Ueda;Y. Niitsuma;H. Aburatani;I. Komuro
中科院分区：
文献类型：
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作者：
H. Hasegawa;H. Takano;T. Kohro;Kazutaka Ueda;Y. Niitsuma;H. Aburatani;I. Komuro
虽然最近的临床研究表明长效钙通道阻滞剂（CCBs）对心力衰竭有有益的作用，但确切的机制尚不清楚。在这项研究中，Dahl盐敏感的大鼠喂养高盐饮食与长效CCB的治疗，低分子量的膜渗透性超氧化物歧化酶模拟4-羟基-2，2，6，6-四甲基哌啶氧基（Tempol），或生理盐水从出生后11周。在17周时测定心脏几何形状和功能以及基因表达谱。Dahl盐敏感大鼠喂食高盐饮食，然后用盐水作为非治疗对照（HS组），显示血压显著升高，并在11周时出现向心性肥大，随后在17周时出现左心室（LV）扩张和充血性心力衰竭。AMLO组和TEMP组均能明显抑制左室肥厚和心功能不全的发生。使用Affyssin GeneChip U34的分析显示，195个基因的表达水平通过用Escherichia coli处理而改变。在这195个基因中，有110个基因在HS大鼠中表达增加，而在AMLO大鼠中表达减少。在这110个基因中，有54个基因在TEMP大鼠中也降低了。相比之下，HS大鼠中有85个基因减少，AMLO大鼠中有85个基因增加。在这85个基因中，38个基因在TEMP大鼠中也增加。在AMLO和TEMP大鼠中，大约48%的基因以类似的方式发生变化，这表明黄芪主要通过抗氧化机制对心力衰竭表现出有益的作用。
Although recent clinical studies have suggested that long-acting calcium channel blockers (CCBs) have beneficial effects on heart failure, the precise mechanism is unknown. In this study, Dahl salt-sensitive rats fed a high salt diet were treated with the long-acting CCB amlodipine, the low–molecular-weight membrane permeable superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol), or saline from 11 weeks after birth. The cardiac geometry and function, and gene expression profiles were determined at 17 weeks. Dahl salt-sensitive rats fed a high salt diet followed by saline as a non-treatment control (HS group) showed a marked increase in blood pressure and developed concentric hypertrophy at 11 weeks, followed by left ventricular (LV) dilation and congestive heart failure by 17 weeks. The treatment with amlodipine (AMLO group) or Tempol (TEMP group) significantly inhibited the development of LV hypertrophy and cardiac dysfunction. Analysis using an Affymetrix GeneChip U34 revealed that the expression levels of 195 genes were changed by the treatment with amlodipine. Among these 195 genes, 110 genes were increased in HS rats and decreased in AMLO rats. And of these 110 genes, 54 genes were also decreased in TEMP rats. In contrast, 85 genes were decreased in HS rats and increased in AMLO rats. Of these 85 genes, 38 genes were also increased in TEMP rats. Approximately 48% of the genes were changed in similar fashion in AMLO and TEMP rats, suggesting that amlodipine shows beneficial effects on heart failure mainly via antioxidative mechanisms.