Enhanced contractile response of the basilar artery to platelet-derived growth factor in subarachnoid hemorrhage

Yoshihisa Maeda, Katsuya Hirano, Mayumi Hirano, Yuichiro Kikkawa, Katsuharu Kameda, Tomio Sasaki, Hideo Kanaide

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background and Purpose-The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH. Methods and Results-A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in [Ca2+];at 1 nmol/L and higher concentrations. The levels of [Ca2+]iand tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K+ depolarization. The PDGF-induced elevation of [Ca2+]i and contraction seen in SAH were abolished in the absence of extracellular Ca2+. In α-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca2+, suggesting no direct effect on myofilament Ca2+ sensitivity. Genistein at 10 /μmol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF. Conclusions-These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca 2+-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.

Original languageEnglish
Pages (from-to)591-596
Number of pages6
JournalStroke
Volume40
Issue number2
DOIs
Publication statusPublished - Feb 1 2009
Externally publishedYes

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Basilar Artery
Platelet-Derived Growth Factor
Subarachnoid Hemorrhage
Phosphorylation
Intracranial Vasospasm
Myosin Light Chains
Myofibrils
Genistein
Tyrosine
Cerebrospinal Fluid

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Enhanced contractile response of the basilar artery to platelet-derived growth factor in subarachnoid hemorrhage. / Maeda, Yoshihisa; Hirano, Katsuya; Hirano, Mayumi; Kikkawa, Yuichiro; Kameda, Katsuharu; Sasaki, Tomio; Kanaide, Hideo.

In: Stroke, Vol. 40, No. 2, 01.02.2009, p. 591-596.

Research output: Contribution to journalArticle

Maeda, Yoshihisa ; Hirano, Katsuya ; Hirano, Mayumi ; Kikkawa, Yuichiro ; Kameda, Katsuharu ; Sasaki, Tomio ; Kanaide, Hideo. / Enhanced contractile response of the basilar artery to platelet-derived growth factor in subarachnoid hemorrhage. In: Stroke. 2009 ; Vol. 40, No. 2. pp. 591-596.
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AU - Kikkawa, Yuichiro

AU - Kameda, Katsuharu

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N2 - Background and Purpose-The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH. Methods and Results-A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in [Ca2+];at 1 nmol/L and higher concentrations. The levels of [Ca2+]iand tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K+ depolarization. The PDGF-induced elevation of [Ca2+]i and contraction seen in SAH were abolished in the absence of extracellular Ca2+. In α-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca2+, suggesting no direct effect on myofilament Ca2+ sensitivity. Genistein at 10 /μmol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF. Conclusions-These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca 2+-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.

AB - Background and Purpose-The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH. Methods and Results-A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in [Ca2+];at 1 nmol/L and higher concentrations. The levels of [Ca2+]iand tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K+ depolarization. The PDGF-induced elevation of [Ca2+]i and contraction seen in SAH were abolished in the absence of extracellular Ca2+. In α-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca2+, suggesting no direct effect on myofilament Ca2+ sensitivity. Genistein at 10 /μmol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF. Conclusions-These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca 2+-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.

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