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• W2074743129 abstract "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." @default.
• W2074743129 created "2016-06-24" @default.
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• W2074743129 date "2011-09-28" @default.
• W2074743129 modified "2023-10-04" @default.
• W2074743129 title "Mechanisms Underlying Potentiation of Endothelin-1-Induced Myofilament Ca²⁺ Sensitization after Subarachnoid Hemorrhage" @default.
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• W2074743129 doi "https://doi.org/10.1038/jcbfm.2011.132" @default.
• W2074743129 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3272600" @default.
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