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Mechanisms Underlying Potentiation of Endothelin-1-Induced Myofilament Ca2+ Sensitization after Subarachnoid Hemorrhage
- Source :
- Journal of Cerebral Blood Flow & Metabolism. 32:341-352
- Publication Year :
- 2011
- Publisher :
- SAGE Publications, 2011.
-
Abstract
- Increased vascular smooth muscle contractility has an important role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Myofilament Ca2+ sensitivity is a major determinant of smooth muscle contractility. We investigated changes in the Ca2+-sensitizing effect of endothelin-1 (ET-1) and the mechanisms underlying ET-1-induced Ca2+ sensitization after SAH using a rabbit SAH model. After SAH, the contractile response to ET-1 was enhanced, and the ETA 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 Ca2+ sensitization is potentiated after SAH. Endothelin-1-induced Ca2+ 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 Ca2+-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 ETA receptor expression are suggested to underlie the enhanced and prolonged Ca2+ sensitization induced by ET-1.
- Subjects :
- Male
Myofilament
medicine.medical_specialty
Vascular smooth muscle
Muscle Proteins
Contractility
Myosin-Light-Chain Phosphatase
Myofibrils
Internal medicine
medicine
Animals
Protein Isoforms
cardiovascular diseases
Phosphorylation
Protein Kinase Inhibitors
Protein Kinase C
Protein kinase C
Sensitization
rho-Associated Kinases
Endothelin-1
business.industry
Vasospasm
Smooth muscle contraction
Subarachnoid Hemorrhage
Phosphoproteins
Receptor, Endothelin A
medicine.disease
Endothelin 1
nervous system diseases
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Neurology
Vasoconstriction
Basilar Artery
Calcium
Original Article
Rabbits
Neurology (clinical)
Cardiology and Cardiovascular Medicine
business
Muscle Contraction
Subjects
Details
- ISSN :
- 15597016 and 0271678X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Accession number :
- edsair.doi.dedup.....d721730b1a589007a1785ad74971700f