AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH)group by injection of CCl4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitroL-arginine (L-NNA)group (n = 21) group, indomethacin (INDO)group (n = 22) and high-dose heparin group (n = 24). The for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-)levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α,a stable hydrolytic product of PGI2, was determined by radioimmunoassay.RESULTS: The concentrations of plasma 6-keto-PGF1α(pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats(1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11,75.21±6.89) were significantly higher than those in SO rats(725.53±105.54, 58.79±8.47) (P＜0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P＜0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1α and serum NO2-/NO3-in IHPH and PHPH rats (P＜0.05) .Meanwhile, CI, FPP and PVI lowered but MAP,TPR and SVR increased(P＜0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters.After administration of high-dose heparin, plasma 6-ketoPGF1α concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle(P＜0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P＜0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P＜0.05), while TPR and SVR increased significantly (P＜0.05).CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.