增加的cGMP提高了微血管运动训练适应能力,独立于内皮氧化合成酶
Nathan C Winn1, David A Cappel1, Ethan D Pollock1
1Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
bioRxiv : the preprint server for biology
|September 30, 2024
概括
通过使用西尔代纳菲尔增强氧化通路,增强了对微血管功能和运动能力的运动益处. 这种组合疗法在改善循环问题患者的运动能力方面表现有前途.
科学领域:
- 心血管生理学心血管生理学
- 运动科学 运动科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 微血管功能受损是糖尿病前期和动脉样硬化的特征,限制行走并增加2型糖尿病的风险.
- 内皮氧化合成酶 (eNOS) /氧化 (NO) /循环瓜诺辛单酸盐 (cGMP) 轴对于调节血管度至关重要.
- 与瘦小鼠相比,饮食诱导肥胖 (DIO) 的小鼠表现出较低的运动能力.
研究的目的:
- 调查是否增强eNOS/NO/cGMP通路可以模仿或增强运动训练对微血管功能和运动能力的益处.
- 测试 eNOS/NO/cGMP 轴的功能与运动训练带来的好处相关的假设.
主要方法:
- 饮食诱导肥胖 (DIO) 的小鼠每天接受西尔代纳菲尔 (一种增加cGMP的PDE-5a抑制剂),以药理上增强eNOS/NO/cGMP轴.
- 使用具有内皮细胞 (EC) 特定的eNOS敲除 (KD) 的瘦小鼠来研究降低的eNOS功能.
- 使用增量运动测试来评估运动能力,并通过测量毛细血管流速和密度的静脉内显微镜来评估微循环功能.
主要成果:
- 在久坐的DIO小鼠中,单独使用西尔代纳菲尔并没有改善运动能力.
- 西尔德纳菲尔与运动训练协同作用,显著提高运动表现,骨肌毛细血管流速和毛细血管密度.
- 在静坐性小鼠中,EC-eNOS KD降低了毛细血管密度和运动耐受性,但并没有阻碍训练诱导的耐力能力改善.
结论:
- 使用西德纳菲尔增加cGMP水平可以增强通过运动训练获得的微循环和运动性能增强.
- 内皮ENOS功能对于提高微循环和耐力能力的运动训练并不重要.
- 将PDE-5a抑制剂与体育炼相结合,为改善循环限制患者的行走提供了一个潜在的策略.
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