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(Stroke. 2009;40:591.)
© 2009 American Heart Association, Inc.

Original Contributions

Enhanced Contractile Response of the Basilar Artery to Platelet-Derived Growth Factor in Subarachnoid Hemorrhage

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

From the Division of Molecular Cardiology, Research Institute of Angiocardiology (Y.M., K.H., M.H., Y.K., K.K., H.K.) and Department of Neurosurgery (Y.M., T.S.), Graduate School of Medical Sciences, and the 21st Century COE program (H.K.), Kyushu University, Fukuoka, Japan.

Correspondence to Katsuya Hirano, MD, PhD, Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail khirano{at}molcar.med.kyushu-u.ac.jp

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⁺]_i at 1 nmol/L and higher concentrations. The levels of [Ca²⁺]_i and 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 -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 Ca²⁺-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.

Key Words: subarachnoid hemorrhage • vasospasm • platelet-derived growth factor