The aim of the study was to investigate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the development of hypoxic pulmonary hypertension. Induction of hypoxic hypoxia in rats resulted in a biphasic increase in systolic right ventricular pressure (RVP). The first phase was transient (5.4 +/- 0.9 min), while the second phase was sustained and persisted during the whole time course of hypoxia (120 min). An inhibition of cNOS with L-NAME (25 mg/kg; i.v.) did not cause any change in the nature of the hypoxic reaction, despite the RVP values were significantly higher in normoxia and hypoxia. These results demonstrate that NO synthase is not substantially involved in the hypoxic pulmonary vasoconstriction. Injection of PKC inhibitor chelerythrine (0.5 mg/kg; i.v.) prevented the development of the first phase of the RVP increase and reduced the second phase by 40%. An inhibition of PC-PLC with D609 (5 mg/kg; i.v.) completely abolished pulmonary hypertension. The results obtained suggest that PC-PLC possibly plays a key role in the development and maintenance of hypoxic pulmonary hypertension.