普罗林因对大鼠中腔动脉产生急性,促收缩的作用
Salomé Rognant1, Samuel N Baldwin1, Harry A T Pritchard2,3
1Department of Biomedical Sciences, University of Copenhagen, Copenhagen N, Denmark.
概括
普罗林因通过抑制大导电性Ca2+激活的K+通道 (BKCa) 并增加细胞内Ca2+释放,增强动脉收缩性. 这种效应涉及前列宁受体 ((P) RR) 和V-ATPase,影响血管光滑肌肉细胞.
科学领域:
- 心血管生理学心血管生理学
- 脏生理学 脏生理学
- 分子生物学分子生物学
背景情况:
- 氨酸及其受体 ((P) RR) 是氨酸-氨酸-氨系统的关键组成部分.
- 普罗林因在血管光滑肌细胞 (VSMC) 收缩性中的作用尚不清楚.
- (P) RR在血管系表达,这表明局部效应.
研究的目的:
- 为了研究前列宁对动脉收缩率的直接影响.
- 为了识别血管光滑肌细胞中的 (P) RR相互作用伙伴.
- 阐明了由前林因介导的血管效应背后的信号机制.
主要方法:
- 在老鼠中腔动脉中进行免疫和近距离结合测定.
- 电线肌图以评估动脉收缩性.
- 在VSMC中的细胞内 ([Ca2+]i) 成像和补丁电生理学.
主要成果:
- 在VSMC中, (P) RR定位在V-ATPase,caveolin-1,瑞诺丁受体和BKCa通道附近.
- 林 (1nM) 强化了α1-上腺受体介导的收缩和增加了Ca2+波.
- 普罗林因抑制了自发的短暂外向电流和BKCa介导的放松,这种效应被V-ATPase抑制所阻止.
结论:
- 普罗林因通过抑制BKCa通道和增加细胞内Ca2+释放来增强动脉收缩性.
- 普罗林因对血管收缩的作用很可能是通过 (P) RR激活,V-ATPase刺激和局部pH变化.
- 这些发现揭示了prorenin在调节血管度方面的新机制.
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