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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)341-352
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

Fingerprint

Myofibrils
Endothelin-1
Subarachnoid Hemorrhage
Myosin-Light-Chain Phosphatase
Protein Kinase C
Intracranial Vasospasm
rho-Associated Kinases
Basilar Artery
Vascular Smooth Muscle
Phosphoric Monoester Hydrolases
Protein Kinases
Smooth Muscle
Up-Regulation
Phosphorylation
Rabbits

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca 2+ sensitization after subarachnoid hemorrhage. / Kikkawa, Yuichiro; Matsuo, Satoshi; Kameda, Katsuharu; Hirano, Mayumi; Nakamizo, Akira; Sasaki, Tomio; Hirano, Katsuya.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 2, 01.02.2012, p. 341-352.

Research output: Contribution to journalArticle

Kikkawa, Yuichiro ; Matsuo, Satoshi ; Kameda, Katsuharu ; Hirano, Mayumi ; Nakamizo, Akira ; Sasaki, Tomio ; Hirano, Katsuya. / Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca 2+ sensitization after subarachnoid hemorrhage. In: Journal of Cerebral Blood Flow and Metabolism. 2012 ; Vol. 32, No. 2. pp. 341-352.
@article{3e434bb9c3f445518d7c87359f3bb050,
title = "Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca 2+ sensitization after subarachnoid hemorrhage",
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.",
author = "Yuichiro Kikkawa and Satoshi Matsuo and Katsuharu Kameda and Mayumi Hirano and Akira Nakamizo and Tomio Sasaki and Katsuya Hirano",
year = "2012",
month = "2",
day = "1",
doi = "10.1038/jcbfm.2011.132",
language = "English",
volume = "32",
pages = "341--352",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca 2+ sensitization after subarachnoid hemorrhage

AU - Kikkawa, Yuichiro

AU - Matsuo, Satoshi

AU - Kameda, Katsuharu

AU - Hirano, Mayumi

AU - Nakamizo, Akira

AU - Sasaki, Tomio

AU - Hirano, Katsuya

PY - 2012/2/1

Y1 - 2012/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84856508603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856508603&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2011.132

DO - 10.1038/jcbfm.2011.132

M3 - Article

VL - 32

SP - 341

EP - 352

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -