Dipyridamole, an Anti-platelet Agent, Reduces the Vascular Endothelial Cell Injury Induced by Active Oxygen Species.
The effects of the anti-platelet agent dipyridamole on vascular endothelial cells were assessed by measurement of the injury index induced by oxygen stress. Vascular endothelial cell injury was assayed by measuring (51)Cr release from labeled vascular endothelial cells. Leukocytes activated by phorbol 12-myristate 13-acetate (PMA) were used to induce the injury of endothelial cells. In this system, dipyridamole suppressed endothelial cell injury in a dose dependent manner (0.1-10 4mUM) while it had no effect on production of superoxide anion in PMA-activated leukocytes. Treatment of endothelial cells with hydrogen peroxide also induced endothelial cell injury in a dose dependent manner (50-150 μM). Dipyridamole also prevented the endothelial cell injury induced by hydrogen peroxide with a dose dependent fashion (1-10 μM). There were no significant changes in the activities of catalyzing enzymes such as catalase and glutathione peroxidase in the endothelial cells following dipyridamole treatment. In contrast, dipyridamole significantly increased the cyclic GMP content of endothelial cells in a dose dependent manner (1-10 μM). Addition of 8-bromo-cyclic GMP (1 mM) to the culture also protected endothelial cells from injury induced by hydrogen peroxide, but 8-bromo-cyclic AMP did not. These data suggest that the protective effect of dipyridamole against oxygen stress is correlated with the increase in the cyclic GMP content of the endothelial cells.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama.
Y
Y
Wakabayashi
H
H
Fujita
K
K
Fujimoto
H
H
Kawaguchi
I
I
Morita
S
S
Murota