BACKGROUND/AIMS: Ischemia/reperfusion is associated with mucosal injury in trauma, rnajor surgery, and nonsteroidal anti-inflammatory drug administration. Nitric oxide and cyclic nucleotides appear to play a cytoprotective role against gastric mucosal injury. Present study was aimed to investigate a cytoprotective mechanism of gastric cells against hypoxia/reoxygenation. METHODS: lsolated gastric cells treated with or without sodium nitroprusside were exposed to hypoxia(30min) /reoxygenation(lh). Histamine(]0'M) with 3-isobuty]-1-methylxanthine(10'M) was used to stimulate acid secretion. Acid secretory activity was measured by [ C]-aminopyrine accumulation ratio. The intracellular cGMP and cAMP were deterrnined by radioimmunoassay. The cell viability was assessed by lactic dehydrogenase release and trypan blue exclusion test. RESULTS: Hypoxia/ reoxygenation inhibited acid secretion, but increased intracellular levels of cGMP and cAMP. Sodium nitroprusside inhibited acid secretion stimulated by histamine and 3-isobutyl- 1-methylxanthine. cGMP level, but not cAMP level, of gastric cells was increased by sodium nitroprusside. Cell viability was neither affected by hypoxia/reoxygenation nor sodium nitroprusside. CONCLUSIONS: Hypoxia/reoxygenation increases cGMP and inhibits acid secretion, possibly through nitric oxide induction, which acts as a mucosal defense mechanism. Increase of cellular cAMP during hypoxic exposure is thought of as cellular adaptation, and this is not re]ated to acid secretion.