二酶1A1表达的升调与酸盐耐受性发展有关
1Department of Medicine, University of Rochester, Rochester, NY, USA.
Circulation
|November 7, 2001
概括
酸盐耐受性可能源于基化酶1A1 (PDE1A1) 活性增加,该活性会降解循环氨酸单酸盐 (cGMP). 抑制PDE1A1可能是克服这种耐受性的新策略.
科学领域:
- 药理学 药理学是指药理学的学科.
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
背景情况:
- 由于耐药性的快速发展,甘 (NTG) 的有效性受到限制.
- NTG产生氧化 (NO),增加循环氨酸单酸盐 (cGMP) 进行血管扩张.
- 增加的固酶 (PDE) 活性降低cGMP是酸盐耐受性的潜在原因.
研究的目的:
- 调查PDE活性在NTG耐受性中的作用.
- 为了确定PDE1A1表达或活性是否随着NTG耐受性而增加.
主要方法:
- 大鼠接受连续NTG输液以诱导耐受性.
- 在大鼠大心脏中分析了PDE活性和PDE1A1表达 (西部斑块,qRT-PCR).
- 用PDE1抑制剂维诺来评估功能恢复.
主要成果:
- NTG耐受性与Ca2+/calmodulin刺激的PDE (PDE1A1) 活性增加有关.
- 由于mRNA上调调节,PDE1A1表达在耐受性老鼠大动脉中增加了2.3倍.
- 维诺素部分恢复了对NTG的血管敏感性,并阻止了 ангиотензинII诱导的cGMP减少.
结论:
- 提高PDE1A1的调节有助于降低酸盐耐受性的NO/cGMP血管扩张.
- 这种机制也可能增强Ca2+介导的血管收缩.
- 向PDE1A1提供了一种潜在的治疗策略,可以预防或逆转酸盐耐受性.
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