NITRIC-OXIDE INDUCES AND INHIBITS APOPTOSIS THROUGH DIFFERENT PATHWAYS

Physiological levels of nitric oxide (NO) regulate vascular tone and p rotect the microvasculature from injury whereas excessive NO may be ha rmful. The present study explored the effects of NO on human endotheli al cell apoptosis, We found that the NO donor S-nitroso-N-acetylpenici llamine (SNAP) inhibited TNF alpha-induced endothelial apoptosis and t hat this was mediated partly through the cGMP pathway. In contrast, hi gh SNAP concentration induced endothelial apoptosis via cGMP-independe nt pathways and the cGMP pathway protected against NO-induced apoptosi s, These findings demonstrate that low NO concentrations contribute to human endothelial cell survival, whereas higher NO concentrations are pathological and promote destruction of endothelial cells. (C) 1998 F ederation of European Biochemical Societies.