Role of PGI2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats.
OBJECTIVE
To investigate the role of prostacyclin (PGI(2)) 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 CCl(4), 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), Nomega-nitro-L-arginine (L-NNA) group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1 mL of saline, L-NNA (3.3 mg/kg.d) and INDO (5 mg/kg.d) respectively through gastric tubes 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 (NO(2)(-)/NO(3)(-)) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1alpha, a stable hydrolytic product of PGI(2), was determined by radioimmunoassay.


RESULTS
The concentrations of plasma 6-keto-PGF1alpha (pg/mL) and serum NO(2)(-)/NO(3)(-) (micromol/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-PGF1alpha and serum NO(2)(-)/NO(3)(-) 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 PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI(2), 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-keto-PGF(1alpha) 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 NO(2)(-)/NO(3)(-) 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).


CONCLUSIONS
It is NO rather than PGI(2) that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.
Wu
Zhi-Yong
ZY
Department of General Surgery, Renji Hospital, 1630 Dongfang Road, Shanghai 200127, China. zhengwk@online.sh.cn
Chen
Xue-Song
XS
Qiu
Jiang-Feng
JF
Cao
Hui
H
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000097:blood*; D006493:Heparin / Q000494:pharmacology; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D019335:Nitroarginine / Q000494:pharmacology; D011168:Portal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology
D000925:Anticoagulants; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D006493:Heparin; D011464:Epoprostenol; D007213:Indomethacin