Exogenous nitric oxide inhibits proliferation of cultured vascular endothelial cells

Cultured bovine fatal aortic endothelial cells (BAECs) were stimulated with nitric oxide (NO)-releasing vasodilators and NO gas-saturated solution, and changes in the cell proliferation were examined. Sodium nitroprusside (SNP) and nitroglycerin (NTG) shifted the growth curve downward, and inhibited 3H-thymidine incorporation by the ECs in a dose-dependent manner. Application of NO solution also reduced 3H-thymidine incorporation. SNP, NTG and NO solution increased the intracellular cGMP in BAECs. A cGMP analog, 8-bromo-cGMP, inhibited 3H-thymidine incorporation, and a guanylate cyclase inhibitor, methylene blue, almost completely blocked the inhibitory effect of SNP and NTG on 3H-thymidine incorporation. These findings suggest that exogenous NO inhibits EC proliferation, and that intracellular cGMP is involved in the inhibitory effect of NO.