卡维地洛对高血压大鼠心肌成纤维细胞一氧化氮合酶-一氧化氮系统的影响
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Effects of Carvedilol on Nitric Oxide Synthase-Nitric Oxide System of Cardiac Fibroblasts in Spontaneously Hypertensive Rats
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    摘要:

    观察基础和卡维地洛干预条件下,自发性高血压大鼠和Wistar大鼠心肌成纤维细胞一氧化氮合酶-一氧化氤系统活性的变化。胰酶消化法分离、培养大鼠心肌成纤维细胞,采用硝酸还原酶法和分光光度法观察基础和卡维地洛干预条件下,培养基中一氧化氮合酶活性及一氧化氮含量的变化。结果发现,在基础状态下72 h,高血压大鼠组心肌成纤维细胞一氧化氮含量(66.6±3 5/μmol/L)及一氧化氮合酶活性(16.7±0.7 kU/L)较Wistar大鼠组(80.8±6.2/μmol/L和29.1±2.1 kU/L)显著降低,并有统计学意义(p<0.01);一氧化氮含量及一氧化氮合酶活性随卡维地洛浓度的增高而增加,均呈别量依赖性;另外,在不同浓度卡维地洛作用下,高血压大鼠组心肌成纤维细胞的一氧化氮含量随一氧化氮合酶活性的增强而增高,二者呈显著正相关(r=0.911,p<0.01)。结果提示,高血压大鼠心肌成纤维细胞的一氧化氮合酶一氧化氮系统功能异常,表现为一氧化氮合酶活性降低,一氧化氮含量减少。卡维地洛使心肌成纤维细胞内一氧化氯合酶一氧化氮系统活性显著增高,并呈浓度依赖性,其中对高血压大鼠的影响远远高于正常血压组,这可能是卡维地洛抑制血压增高的重要机制之一。

    Abstract:

    Aim To evaluate the changes of nitric oxide synthase-nitric oxide system activity in rat cardiac fibroblasts (CF) derived from spontaneously hypertensive rat (SHR) and Wistar rat with and without carvedilol. Methods CF were iso-lated by trypsin digestion method. Nitric acid reductase method and spectrophotometry were used to detect the NO contents and NOS activity respectively with or without carvedilol. Results Under basal condition (72 h), NO content (66.6 ± 3.5 μmol/ L)ancl NOS activity (16.7 ± 0.7 kU/L)of CF derived from SHR were siginificantly lower than those of Wistar rats (80. 8 ± 6.2 μmol/L, 29.1 ± 2. 1 kU/L) ( P< 0.01) . Carvedilol could significantly increase NOS activity and NO content of CF derived from two groups, which showed dose-dependent effects. Moreover, NO contents increased with the enhancement of NOS activity, and there was significant positive relevance between them ( r = 0.911, P< 0.01) . Conclusion The NOS-NO system of CFin SHR was abnormal, which showed that NOS activity and NO content of CF in SHR were lower. Carvedilol could significantly increase NOS activity and NO content of CF derived from two groups, but the effect on CF of SHR was much more powerful than that of Wistar rats. The effect may be an important mechanism to control blood pressure.

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张海涛,赵连友,刘朝中,罗慧兰,王荫静,于心亚,田建伟.卡维地洛对高血压大鼠心肌成纤维细胞一氧化氮合酶-一氧化氮系统的影响[J].中国动脉硬化杂志,2004,12(3):321~324.

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  • 收稿日期:2003-10-20
  • 最后修改日期:2004-05-16
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