Enhanced contractile response of the basilar artery to platelet-derived growth factor in subarachnoid hemorrhage.
OBJECTIVE
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
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 [Ca(2+)](i) at 1 nmol/L and higher concentrations. The levels of [Ca(2+)](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 [Ca(2+)](i) and contraction seen in SAH were abolished in the absence of extracellular Ca(2+). In alpha-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca(2+), suggesting no direct effect on myofilament Ca(2+) sensitivity. Genistein at 10 micromol/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.
Maeda
Yoshihisa
Y
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hirano
Katsuya
K
Hirano
Mayumi
M
Kikkawa
Yuichiro
Y
Kameda
Katsuharu
K
Sasaki
Tomio
T
Kanaide
Hideo
H
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D010982:Platelet-Derived Growth Factor; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium