蛋白质激酶C epsilon有助于慢性机械反射敏感性在心力衰竭的老鼠
Alec L E Butenas1, Shannon K Parr1, Joseph S Flax1
1Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
The Journal of physiology
|September 13, 2024
概括
蛋白质激酶Cepsilon (PKCε) 信号传递,而不是内醇三酸盐 (IP3) 受体,有助于在心力衰竭的老鼠中增加同情神经活动,心力衰竭减少排泄率 (HF-rEF). 这一发现对于了解HF-rEF患者心血管风险至关重要.
科学领域:
- 心血管生理学心血管生理学
- 神经科学是一个神经科学.
- 细胞信号传递 细胞信号传递
背景情况:
- 减少喷射分数 (HF-rEF) 的心力衰竭与运动期间过度的交感神经活动有关.
- 这种交感过度活动可能源于肌肉附属体的慢性敏感化,可能涉及Gq蛋白结合受体.
- 在HF-rEF中调解这种敏感化的特定细胞内信号通路尚不清楚,因诺西1,4,5-三酸盐 (IP3) 受体和蛋白激酶Cepsilon (PKCε) 是潜在的候选者.
研究的目的:
- 研究IP3受体和PKCε在患有HF-rEF的老鼠肌肉 afferents的慢性机械反射敏感化中的作用.
- 为了确定阻断这些信号组件是否会降低交感神经活动 (RSNA) 和平均动脉压 (MAP) 对肌肉伸展的反应,在HF-rEF.
主要方法:
- 使用了去脑动物,未经麻醉的老鼠与手术诱导的HF-rEF和假操作的对照.
- 将IP3受体对抗剂克斯托斯丁C或PKCε转位抑制剂PKCe141注入后肢动脉供应.
- 测量了RSNA和MAP对后肢肌肉动态拉伸的反应,在药物服药前后.
主要成果:
- 在HF-rEF大鼠中,IP3受体阻断没有改变肌肉伸展期间RSNA或MAP的增加.
- 相反,PKCε抑制显著降低了HF-rEF大鼠对肌肉伸展的夸张RSNA和MAP反应.
- 两种药物都没有影响假操作对照大鼠的机械反射反应.
结论:
- PKCε,但不是IP3受体,是一个重要的第二信使,参与HF-rEF中的慢性机械反射敏感化.
- 这些发现确定PKCε是HF-rEF运动过度同情反应的关键参与者.
- 准PKCε信号可能提供一种治疗策略,以减轻与HF-rEF相关的心血管风险.
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