NITRIC-OXIDE PROTECTS ENDOTHELIAL-CELLS FROM TUMOR-NECROSIS-FACTOR-ALPHA MEDIATED CYTOTOXICITY - POSSIBLE INVOLVEMENT OF CYCLIC-GMP

In cultured endothelial cells, incubation with TNF-a (50 ng/ml) for 48 h markedly reduced viability of endothelial cells. A 6 h preincubatio n with Sper/NO (0.03-1 mu M) protected endothelial cells in a concentr ation-dependent manner and increased viability by 63% of control. The NO scavenger PTIO (30 mu M) completely abolished cytoprotection by Spe r/NO. A cytoprotective effect comparable to Sper/NO was observed when preincubating the cells with 8-bromo cyclic GMP (1-10 mu M). Moreover, no protection by Sper/NO occurred in the presence of ODQ (0.1 mu M), a selective inhibitor of soluble guanylyl cyclase. Our results demonst rate that NO produces a long-term endothelial protection against cellu lar injury by TNF-alpha, presumably via a cyclic GMP-dependent pathway . (C) 1997 Federation of European Biochemical Societies.