Ca2+ channel blocker benidipine promotes coronary angiogenesis and reduces both left-ventricular diastolic stiffness and mortality in hypertensive rats
Ca2+ channel blocker benidipine promotes coronary angiogenesis and reduces both left-ventricular diastolic stiffness and mortality in hypertensive rats
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DOI：
10.1097/hjh.0b013e328339fd3a
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发表时间：
2010-07-01
影响因子：
4.9
通讯作者：
Murohara, Toyoaki
中科院分区：
文献类型：
--
作者：
Nishizawa, Takao;Cheng, Xian Wu;Murohara, Toyoaki
背景：一些钙通道阻滞剂的有益心脏作用归因于降压，但这些多效性作用还需要进一步研究。在高血压舒张性心力衰竭(DHF)动物模型中，我们比较了有益心脏作用的贝尼地平和非尼群地平的作用。方法和结果雄性Dahl盐敏感大鼠从7周龄开始给予高盐饮食诱发高血压，从10周龄到18周龄分别口服或注射贝尼地平(3 mg/kg，每日3 mg/kg)或尼群地平(10 mg/kg，每天10 mg/kg)。对照组大鼠保持低盐饮食。在赋形剂治疗的大鼠中，左室短轴缩短率(LV)被保留下来，但LV舒张末压力升高，这表明DHF。贝尼地平和尼群地平具有相似的降压作用，均能减轻左心室重量和心肌细胞肥大。与尼群地平相比，贝尼地平能更大程度地降低左心室舒张期僵硬度和死亡率。贝尼地平，但不是尼群地平，也减轻了肺重量。贝尼地平和尼群地平可减轻间质纤维化的程度和左心室肥大、纤维化或促炎基因的mRNAs丰度。贝尼地平可增加心肌毛细血管密度，并恢复低氧诱导因子1α、血管内皮生长因子和内皮型一氧化氮合酶的表达，但尼群地平无此作用。结论贝尼地平可降低左心室舒张期僵硬，提高存活率，其作用机制可能主要是促进冠状动脉新生血管生成，而不是减轻间质纤维化。因此，贝尼地平在预防高血压DHF方面可能比单纯的L类钙通道阻滞剂更有效。J Hyperten 28：1515-1526(C)2010沃尔特斯·克鲁沃健康垂直酒吧Lippincott Williams&Wilkins。
Background The beneficial cardiac effects of some Ca2+ channel blockers have been attributed to blood pressure reduction, but these pleiotropic effects require further investigation. We compared the effects of benidipine, which has beneficial cardiac effects, and nitrendipine, which does not, in an animal model of hypertensive diastolic heart failure (DHF).Methods and results Male Dahl salt-sensitive rats were fed a high-salt diet from age 7 weeks to induce hypertension and were either vehicle or orally administered benidipine (3 mg/kg daily) or nitrendipine (10 mg/kg daily) from age 10 to 18 weeks. Control rats were maintained on a low-salt diet. In vehicle-treated rats, left-ventricular (LV) fractional shortening was preserved but LV end-diastolic pressure was increased, indicative of DHF. Benidipine and nitrendipine had similar antihypertensive effects and reduced both LV weight and cardiomyocyte hypertrophy. Benidipine reduced LV diastolic stiffness and mortality to a greater extent than did nitrendipine. Benidipine, but not nitrendipine, also reduced lung weight. The extent of interstitial fibrosis and the abundance of mRNAs for prohypertrophic, profibrotic, or proinflammatory genes in the left ventricle were reduced by benidipine and nitrendipine. Benidipine, but not nitrendipine, increased capillary density and restored the expression of hypoxia-inducible factor 1 alpha, vascular endothelial growth factor, and endothelial nitric oxide synthase in the left ventricle.Conclusions Benidipine reduced LV diastolic stiffness and increased survival, effects likely attributable predominantly to promotion of coronary angiogenesis rather than to attenuation of interstitial fibrosis. Benidipine may thus be more effective than purely L-type Ca2+ channel blockers in preventing hypertensive DHF. J Hypertens 28:1515-1526 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.