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血管紧张素瞬间及持续刺激对乳鼠培养心肌细胞内游离钙的影响

Effects of Transient and Sustained Stimulation of Angiotensin on Cytosolic Free Calcium in Neonatal Rat Cardiomyocytes
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摘要 应用双波长微荧光检测技术研究血管紧张素瞬间及持续刺激对乳鼠培养心肌细胞内游离钙的影响。结果显示,当加入血管紧张素Ⅱ(Ang Ⅱ)(10^(-10)mol/L)时,可观察到一个瞬间上升波峰,继而恢复,钙搏动振幅及频率无明显改变。加入Ang Ⅱ(10^(-8)mol/L)时,出现一个较为陡直的上升支,且有钙搏动频率加快,振幅增大。当Ang Ⅱ的加入量增至10^(-6)mol/L时,舒张期胞内钙浓度[Ca^(2+)]i明显增高达374.6±8.2nmol/L,与给药前95.7±8.4nmol/L比较差异有极显著性(P<0.01),并呈现约几十秒钟的Ca^(2+)静止期。说明Ang Ⅱ可诱发胞内钙浓度的瞬间增高,且随剂量的不同表现为正性肌力和负性肌力两种作用。Ang Ⅱ对胞内钙的影响可被选择性的AT_1受体亚型拮抗剂DuP753所消除,但Ang Ⅱ受体亚型拮抗剂PD123319对Ang Ⅱ的作用无影响。阻滞电压依赖性Ca^(2+)通道可降低胞内钙浓度,但仅能部分地减少Ang Ⅱ对Ca^(2+)的影响。内质网Ca^(2+)-ATP酶抑制剂thapsigargin可降低或消除Ca^(2+)对Ang Ⅱ的反应,因此,Ang Ⅱ瞬间刺激所诱发的胞内游离Ca^(2+)的变化主要取决于内质网的Ca^(2+)释放。Ang Ⅱ和AngⅠ持续刺激均能使心肌细胞内Ca^(2+)升高,且随时间延长而递增。AngⅡ受体拮抗剂和转换酶抑制剂可消除或减弱二者的作用。说明心肌? The effects of transient and continuous stimulation of angiotensin Ⅱ (Ang Ⅱ) on cytosolic free Ca2+ concentration ([Ca2+]i) was studied in cultured neonatal rat ventricular myocytes. [Ca2+]i was estimated by dual-wave length microfluorometry. The results showed that when Ang Ⅱ 10-10mol/L was added, transient ascendant wave crest was observed. After exposed to Ang Ⅱ(10-8 mol/L), the steep wave crest occurred and the frequency and amplitude of Ca2+ transients were increased. Diastolic [Ca2+]i was increased to 374. 6±8. 2 nmol/L when Ang Ⅱ (10-8mol/L) was added. There was a cessation of the [Ca2+]i. These indicated that Ang Ⅱ induced the increase of [Ca2+]i and both positive and negative in-otropic effects were found depending on the dosage. The effect of Ang Ⅱ on [Ca2+]i was blocked by the selective AT1 receptor subtype antagonist DuP753 but not by the AT2 antagonist PD 123319. Removal of extracellular Ca2+ or blockade of voltage-gated Ca2+ channels reduced the [Ca2+]i transients, but only partially diminished the effect of Ang Ⅱ on [Ca2+]i. Thapsigargin, an inhibitor of sarcoplasmic reticulum Ca2+-ATPase, completely abolished the [Ca2+]i response to Ang Ⅱ. Thus Ang Ⅱ produced an acute rise in [Ca2+]i which is derived predominantly from sarcoplasmic reticulum intracellular stores. Sustained stimulation by both Ang Ⅱ and Ang Ⅰ increased cytosolic [Ca2+]i. The effect was increased with the duration of stimulation. Ang Ⅱ receptor antagonist and angiotensin converting enzyme (ACE) inhibitor reduced or abolished the both above effects. It is sug-gested that cardiomyocytes have the function to secrete ACE itself.
出处 《高血压杂志》 CSCD 1995年第4期266-269,共4页 Chinese Journal of Hypertension
关键词 血管紧张素 心肌细胞 药理学 angiotensin myocardial cell culture intracel-lular free calcium Fura-2/AM
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参考文献2

  • 1田斌,卢兴,陈雁群,程薇.血管紧张素在培养乳鼠心肌细胞肥大发生中的作用[J]中国病理生理杂志,1991(02).
  • 2O. Thastrup,A. P. Dawson,O. Scharff,B. Foder,P. J. Cullen,B. K. Dr?bak,P. J. Bjerrum,S. B. Christensen,M. R. Hanley. Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage[J] 1989,Agents and Actions(1-2):17~23

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