肌细胞氧化合成酶2通过减少Ca2+短暂物质,有助于在失败的人类心脏中减弱β-上腺素反应
Mark T Ziolo1, Lars S Maier, Valentino Piacentino
1Department of Physiology, Loyola University Medical Center, Maywood, Ill 60153, USA.
Circulation
|March 24, 2004
概括
在人类心力衰竭中,氧化合成酶-2 (NOS2) 限制了对β-上腺刺激的反应. 抑制NOS2会恢复这种反应,这表明NOS2在心力衰竭中调解β-AR低响应性.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 身体生理学 身体生理学
背景情况:
- 人类心力衰竭 (HF) 的特征是对β-上腺素受体 (AR) 刺激的反应减弱.
- 氧化合成酶-2 (NOS2) 在这种麻木反应中的作用尚不清楚.
研究的目的:
- 调查NOS2表达是否有助于人类HF的内储备的丧失.
- 为了确定NOS2抑制是否可以恢复失败的人类心脏中的β-AR反应能力.
主要方法:
- 在移植过程中获得了人类失败和不失败的心脏.
- 测量了心脏肌细胞和轨道细胞收缩性和细胞内 ([Ca2+]i) 过渡物.
- 评估了β-ARagonist异二烯醇 (ISO) 和NOS2抑制剂 (aminoguanidine或L-NIL) 的作用.
主要成果:
- 在失败的心脏中,ISO产生了最小的内热和热效应.
- 抑制NOS2显著增强了ISO诱导的收缩性和[Ca2+]i过渡物,接近在非失败的心脏中看到的水平.
- 在心力衰竭患者中,NOS2蛋白表达升高,而抑制则具有功能效应.
结论:
- 在人类HF中,NOS2表达显著限制了β-AR介导的收缩性和处理的增加.
- 人类HF中的β-AR低响应性在很大程度上是由心肌细胞内通过NOS2产生的氧化调解的.
关键词:
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