Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice
Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice
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DOI：
10.1016/j.cardiores.2004.11.006
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发表时间：
2005-03-01
影响因子：
10.8
通讯作者：
Kitakaze, M
中科院分区：
文献类型：
--
作者：
Liao, YL;Asakura, M;Kitakaze, M
目的：长效钙通道阻滞剂（CCB）对压力超负荷性心脏重构的影响在动物实验中的研究较少。我们评价了贝尼地平，一种长效CCB，对心脏重构的影响。方法：采用新生大鼠心肌细胞，研究贝尼地平对蛋白质合成的影响。用横主动脉缩窄法（TAC）诱导C5 7 B6/J小鼠心脏重构。结果：贝尼地平（10 mg/kg/d）可明显抑制苯肾上腺素（PE）刺激的心肌细胞蛋白质合成，而一氧化氮合酶（NOS）抑制剂[N（G）-硝基-L-精氨酸甲酯（L-NAME）]可部分阻断贝尼地平的抑制作用。在压力超负荷发作四周后，贝尼地平治疗有效地抑制了心脏肥大，防止了心力衰竭。治疗组小鼠的心脏与体重的比值为6.89 +/- 0.48 mg/g，而未治疗组小鼠为8.76 +/- 0.33 mg/g（P <0.05）。
Objective: The effects of long-acting calcium channel blockers (CCBs) on pressure overload-induced cardiac remodeling are seldom studied in animals. We evaluated the effects of benidipine, a long-acting CCB, on cardiac remodeling.Methods: Rat neonatal cardiac myocytes were used to examine the influence of benidipine on protein synthesis. Cardiac remodeling was induced in C5 7 B6/J mice by transverse aortic constriction (TAC). Then the effects of benidipine (10 mg/kg/d) were assessed on myocardial hypertrophy and heart failure, cardiac histology, and gene expression.Results: Benidipine significantly inhibited protein synthesis by cardiac myocytes stimulated with phenylephrine (PE), and this effect was partially abolished by cotreatment with a nitric oxide synthase (NOS) inhibitor [N(G)-nitro-L-arginine methylester (L-NAME)]. Four weeks after the onset of pressure overload, benidipine therapy potently inhibited cardiac hypertrophy and prevented heart failure. The heart to body weight ratio was 6.89 +/- 0.48 mg/g in treated mice vs. 8.76 +/- 0.33 mg/g in untreated mice (P