Effects of nitric oxide inhibitor on prostacyclin biosynthesis in portal hypertensive rats.
OBJECTIVE
To evaluate the effects of nitric oxide inhibitor on prostacyclin (PGI2) biosynthesis and the role of PGI2 in hyperhemodynamics of portal hypertension.


METHODS
Sprague Dawley rats were divided into four groups: intrahepatic portal hypertension (IHPH) by injection of CCl4, prehepatic portal hypertension (PHPH) by stenosis of the portal vein, end-to-side portacaval shunt (PCS), and sham-operated controls (SO). Animals of each group were subdivided into 2 groups: systemic administration of nitric oxide inhibitor L-NMMA and vehicle. The radioactive microsphere method was used for hemodynamic study. The level of plasma PGI2 (6-keto-PGF1 alpha) was measured by radioimmunoassay.


RESULTS
The characteristics of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance, and splanchnic vascular resistance were observed in IHPH, PHPH and PCS rats. The magnitude of hyperhemodynamics was in the order of PCS > PHPH > IHPH rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L-NMMA to the baseline values of hemodynamics in SO rats. The baseline concentrations of plasma 6-keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS, and SO rats were 6.93 +/- 2.43, 5.09 +/- 2.27, 2.36 +/- 1.01 and 1.56 +/- 0.61, respectively. The concentrations of plasma 6-Keto-PGF1 alpha in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Moreover, the concentrations were significantly higher in PHPH and IHPH rats than in PCS rats (P < 0.05). After administration of L-NMMA, the concentrations of plasma 6-Keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS and SO rats were 7.69 +/- 2.98, 5.68 +/- 2.66, 5.50 +/- 0.79, 5.02 +/- 2.86, respectively. As compared to the baseline value, the concentrations of 6-keto-PGF1 alpha rats were slightly increased in IHPH, PHPH rats (P > 0.05), but significantly increased in PCS and SO rats (P < 0.05).


CONCLUSIONS
In this study, the hyperdynamic circulatory state in portal hypertensive rats and portacaval shunt rats was completely reversed by L-NNMA to normal, but the level of 6-keto-PGF1 alpha was still elevated. The results indicate that PGI2 is not involved in hyperhemodynamics of portal hypertension.
Cao
H
H
Department of Surgery, Ren Ji Hospital, Shanghai Second Medical University, Shanghai 200001, China.
Wu
Z
Z
Zhou
J
J
Chen
Z
Z
Kuang
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D019001:Nitric Oxide Synthase