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.