Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were investigated to determine effects on apoptotic DNA fragmentation and survival in serum-deprived PC12 cells. Both peptides caused prolonged cGMP (but not cAMP) elevations lasting for > or = 6 h. The cGMP elevations were 10-, 50- and 68-fold for ANP and 26-, 100- and 148-fold for BNP at 1, 10 and 100 nM, respectively. BNP caused dose-dependent increases in cell survival rates during 3 days of serum deprivation. BNP (1 nM) increased 24 h survival rate from 36% to 67%. ANP (1 nM), BNP (1 nM) and 8-bromo-cGMP (0.1 mM) inhibited by 74.8%, 46.7% and 86.8%, respectively, the apoptotic DNA fragmentation in serum-deprived PC12 cells, measured by our recently developed quantitative technique using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). The data suggest prolonged cGMP elevations caused by ANP or BNP inhibit apoptotic DNA fragmentation and prolong the survival of serum-deprived PC12 cells.