在一次性和二次性高血压中对Kv7.4通道活性进行下调
Thomas A Jepps1, Preet S Chadha, Alison J Davis
1Division of Biomedical Sciences, St. George's, University of London, United Kingdom.
Circulation
|July 13, 2011
概括
电压通道 (Kv7通道) 调节血管度,但在高血压模型中是下调的. 这项研究研究了高血压大鼠和小鼠的Kv7通道功能,发现反应受损和Kv7.4蛋白水平降低.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 由KCNQ基因 (Kv7通道) 编码的电压关闭通道是血管血管调节的关键调节者.
- 在血管疾病中Kv7通道的功能影响仍然在很大程度上不明.
研究的目的:
- 确定三个结构不同的Kv7通道激活剂 (BMS-204352,S-1和 retigabine) 对正常血压和高血压动物的血管的影响.
- 在高血压模型中研究Kv7通道的功能影响和表达.
主要方法:
- 血管放松和冠状动脉输液研究使用胸前大动脉,中腔动脉细分以及来自正常血压和自发高血压大鼠 (SHRs) 的兰登多夫心脏制剂进行.
- 在隔离的中腔动脉肌细胞中测量了电流.
- 分析了KCNQ基因和Kv7.4蛋白的表达水平在正常血压和高血压的老鼠和小鼠的血管组织中.
主要成果:
- 这三种Kv7激活剂都放松了预先收缩的血管,并在不同强度的正常血压动物中增加了冠状动脉输液.
- Kv7激活剂放松血管,增加冠状动脉流动和增加K(+) 电流的能力在SHRs和输血酶II注入小鼠的组织中显著受损.
- KCNQ4基因表达减少,Kv7.4蛋白水平在高血压大鼠和小鼠的血管组织中明显较低,与正常血压对照相比.
结论:
- 在两种不同的大鼠和小鼠高血压模型中,Kv7通道的功能影响显著下调.
- 降低的Kv7.4蛋白水平和受损的通道功能有助于高血压的血管功能障碍.
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