Endothelial dysfunction and altered bradykinin response due to oxidative stress induced by serum deprivation in the bovine cerebral artery.

Oxidative stress plays a critical role in the pathogenesis of vasospasm after a subarachnoid hemorrhage. We demonstrate that 24-h incubation of the isolated bovine middle cerebral arteries in the serum-free media at 37 degrees C converted the response to bradykinin from relaxation to contraction, in a manner sensitive to free radical scavengers. In the freshly prepared strips, bradykinin induced an endothelium-dependent relaxation, while having no direct effect on the smooth muscle. However, in the strips treated in serum-free media, bradykinin failed to induce endothelium-dependent relaxation, but did demonstrate a direct contractile effect on smooth muscle. The addition of superoxide dismutase and ascorbic acid or 5% serum during the 24-h incubation in the serum-free media prevented the loss of endothelium-dependent relaxation and the development of a contractile response to bradykinin. SB203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole), a p38 mitogen-activated protein kinase inhibitor, and genistein (4',5,7-Trihydroxyisoflavone), a tyrosine kinase inhibitor, also demonstrated a similar preventive effect. In conclusion, serum-deprivation induced endothelial dysfunction and the responsiveness of smooth muscle to bradykinin due to failure of eliminating oxidative stress. p38 mitogen-activated protein kinase and tyrosine kinase were suggested to play a critical role in this endothelial dysfunction.