Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca 2+ sensitization after subarachnoid hemorrhage

Yuichiro Kikkawa, Satoshi Matsuo, Katsuharu Kameda, Mayumi Hirano, Akira Nakamizo, Tomio Sasaki, Katsuya Hirano

研究成果: Contribution to journalArticle査読

15 被引用数 (Scopus)

抄録

Increased vascular smooth muscle contractility has an important role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Myofilament Ca 2+ sensitivity is a major determinant of smooth muscle contractility. We investigated changes in the Ca 2+-sensitizing effect of endothelin-1 (ET-1) and the mechanisms underlying ET-1-induced Ca 2+ sensitization after SAH using a rabbit SAH model. After SAH, the contractile response to ET-1 was enhanced, and the ET A receptor expression was upregulated in the basilar artery. In α-toxin-permeabilized preparations, ET-1 induced enhanced and prolonged contraction after SAH, suggesting that ET-1-induced Ca 2+ sensitization is potentiated after SAH. Endothelin-1-induced Ca 2+ sensitization became less sensitive to inhibitors of Rho-associated coiled-coil protein kinase (ROCK) and protein kinase C (PKC) after SAH. The expression of PKCα, ROCK2, PKC-potentiated phosphatase inhibitor of 17 kDa (CPI-17) and myosin phosphatase target subunit 1 (MYPT1) was upregulated, and the level of phosphorylation of CPI-17 and MYPT1 was elevated after SAH. This study demonstrated for the first time that the Ca 2+-sensitizing effect of ET-1 on myofilaments is potentiated after SAH. The increased expression and activity of PKCα, ROCK2, CPI-17, and MYPT1, as well as the upregulation of ET A receptor expression are suggested to underlie the enhanced and prolonged Ca 2+ sensitization induced by ET-1.

本文言語英語
ページ(範囲)341-352
ページ数12
ジャーナルJournal of Cerebral Blood Flow and Metabolism
32
2
DOI
出版ステータス出版済み - 2 2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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