AGE-RELATED CHANGES IN THE CARDIAC RESPONSE TO ENDOTHELIN-1 AND THE RECEPTOR IN RAT VENTRICULAR MYOCARDIUM.

大鼠心室心肌内皮素-1 和受体的心脏反应与年龄相关的变化。

基本信息

  • 批准号:
    08838001
  • 负责人:
  • 金额:
    $ 1.41万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1997
  • 项目状态:
    已结题

项目摘要

Endothelin (ET) is an endogenous potent vasoconstrictor, which may be involved in the pathogenesis of various cardiovascular diseases. It has been known that a high density of ET receptors is found in mammalian myodardium and myocardial ET receptors are up-regulated in some pathologic states. We have found that ET-1-induced coronary vasoconstriction increased with age and myocardial ET receptors are up-regulated in aged rat in compare with young rat.In this study we examined the mechanisms of the age-related changes in the cardiac response to ET-1 and gene expression of ET^A-and ET^B-receptors as well as age-related changes in the binding characteristics of ET receptor in rat ventricular myocardium.Results : In experiments with isolated papillary muscles, ET-1 elicited a positive inotropic effect in the young rat, but not in aged rat. A SR-Ca-ATP ase inhibitor, cyclopiazonic acid, concentration-dependently inhibited the positive inotropic effects in the young rat. Receptor assay showed that the affinity of ET-receptor was not age-related differences, but the density (Bmax) of ET-binding was significantly increased in aged rats. Gene expression of both ET^A-and ET^B-receptors determined by Northern blotting analysis or semiquantitative RT-PCR increased in aged rats, but not significantly. The ratio of ET^A-and ET^B-receptors mRNA was not changed, suggesting that the alteration of responsiveness to ET is not due to the change in the ratio of ET^A-and ET^B-receptors. These findings suggest that the decrease in the function of SR Ca-ATP ase may be responsible for the marked attenuation of the ET-induced positive inotropic effects in the aged rat. Alternatively the increase in ET-receptor in aged rats may be an adaptation to decreased cardiac responsiveness to ET-1.
内皮素(ET)是一种内源性有效的血管收缩剂,可能与各种心血管疾病的发病机理有关。众所周知,在哺乳动物肌心肌中发现了高密度的ET受体,在某些病理状态下,心肌ET受体被上调。 We have found that ET-1-induced coronary vasoconstriction increased with age and myocardial ET receptors are up-regulated in aged rat in compare with young rat.In this study we examined the mechanisms of the age-related changes in the cardiac response to ET-1 and gene expression of ET^A-and ET^B-receptors as well as age-related changes in the binding characteristics of ET receptor in rat ventricular myocardium.Results : In分离的乳头肌肉的实验ET-1引起了年轻大鼠的阳性肌力作用,但在老年大鼠中没有引起阳性。 SR-CA-ATP ASE抑制剂环皮二唑酸浓度依赖性地抑制了年轻大鼠的阳性肌力作用。受体分析表明,ET受体的亲和力不是与年龄相关的差异,但是老年大鼠的ET结合的密度(BMAX)显着增加。通过北印迹分析或半定量RT-PCR确定的ET^a和et^b受体的基因表达在老年大鼠中增加,但没有显着。 Et^a-and et^b受体mRNA的比率没有改变,这表明对ET的反应性的改变不是由于Et^a-and et^b受体比率的变化所致。这些发现表明,SR CA-ATP ASE功能的下降可能是造成ET诱导的老年大鼠阳性正性效应的明显衰减的原因。或者,老年大鼠ET受体的增加可能是对降低对ET-1的心脏反应性的适应性。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Akira Ishihata: "Aging-associated adaptation of the rat heart by increased expression of the endothelin-receptors." Cardiac Structure and Metabolism. 20(in press). (1998)
Akira Ishihata:“通过增加内皮素受体的表达来实现与衰老相关的大鼠心脏的适应。”
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    0
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  • 通讯作者:
Zhe-Long XU: "Effect of ischemic preconditioning on myocardial oxygen consumption durihg ischemi a." J.Mol.Cell Cadiol.(印刷中). (1998)
徐哲龙:“缺血预处理对缺血期间心肌耗氧量的影响。”(J.Mol.Cell Cadiol)(出版中)。
  • DOI:
  • 发表时间:
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    0
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  • 通讯作者:
Akira Ishihata: "Inhibition of the expression of the gene for the angiotensin ATl receptor by angiotensin II in the rat adredel gland." European J. Pharmacol. (印刷中). (1998)
Akira Ishihata:“血管紧张素 II 在大鼠 adredel 腺中抑制血管紧张素 AT1 受体基因的表达”,European J. Pharmacol(出版中)。
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yumi Katano: "Age-related changes in the contractile response to endothelin-1 and in binding characteristics of the endothelin receptor in rat ventricular myocardium." The Developing Heart.301-310 (1997)
Yumi Katano:“大鼠心室心肌内皮素-1 收缩反应和内皮素受体结合特征与年龄相关的变化。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Zhe-Long Xu: "Effect of ischemic preconditioning on myocardial oxygen consumpting during ischemia." J,Mol,Cell,Cardiol.(印刷中). (1998)
徐哲龙:“缺血预处理对缺血期间心肌耗氧量的影响”,J,Mol,Cell,Cardiol。(出版中)。
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    0
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KATANO Yumi其他文献

KATANO Yumi的其他文献

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{{ truncateString('KATANO Yumi', 18)}}的其他基金

The importance of hypertriglyceridemia in progressof atherosclerosis
高甘油三酯血症在动脉粥样硬化进展中的重要性
  • 批准号:
    19590239
  • 财政年份:
    2007
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanism of impairment of NO production by aging and trials for the amelioration of endothelial function
衰老导致 NO 产生受损的机制以及改善内皮功能的试验
  • 批准号:
    15590220
  • 财政年份:
    2003
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
THE MECHANISM OF AGE-RELATED CHANGES IN THE RELEASE OF NITRIC OXIDE.
一氧化氮释放与年龄相关的变化机制。
  • 批准号:
    11670658
  • 财政年份:
    1999
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of aging-associated genes in myocardium : application of RT-PCR differential display method.
心肌衰老相关基因分析:RT-PCR差异显示法的应用。
  • 批准号:
    09557008
  • 财政年份:
    1997
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Functional relevance of the changes in cyclic AMP accumulation.
环 AMP 积累变化的功能相关性。
  • 批准号:
    03670090
  • 财政年份:
    1991
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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