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

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.