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Influence of nitric oxide synthase and cyclooxygenase blockade on expression of cyclooxygenase and hemodynamics in rats with portal hypertension |
Hui Cao, Jia Xu, Hua Liu, Fang-Bin Meng, Jiang-Feng Qiu and Zhi-Yong Wu |
Shanghai, China
Author Affiliations: Department of Surgery, Renji Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200127, China (Cao H, Xu J, Liu H, Meng FB, Qiu JF and Wu ZY)
Corresponding Author: Hui Cao, MD, Department of Surgery, Renji Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200127, China (Tel: 86-21-58752345; Email: xujia201800@126.com) |
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Abstract BACKGROUND: The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyperdynamic circutatory state in PHT has not been verified. The present study was undertaken to investigate the possible interaction between prostacyclin (PGI2) and nitric oxide (NO) in the hyperdynamic circulatory state of rats with chronic portal hypertension (PHT), by measuring the hemodynamic changes and expression of cyclooxygenase (COX) mRNA in vessels and small intestine after administration of Nω-nitro-L-arginine (L-NNA) or indomethacin (INDO) either in the short-term (7 days) or long-term (15 days).
METHODS: Ninety-seven male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4, prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein, and sham-operated controls (SO). Animals of each group received L-NNA or INDO either for 7 or 15 days, with saline as control. Splanchnic hemodynamics was measured by the radioactive microsphere technique. The concentration of NO in serum was determined as the nitrate; nitrite ratio (NO2-/NO3-, µmol/L) by a colorometric method, and that of PGI2 was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α (pg/ml). The reverse transcription-polymerase chain reaction measured the levels of COX-1 mRNA in the superior mesenteric artery, thoracic aorta, and small intestine of these rats.
RESULTS: Compared with SO rats, COX-1 mRNA expression and the concentrations of plasma 6-keto-PGF1α and serum NO2-/NO3- were enhanced in both IHPH and PHPH rats; splanchnic vascular resistance (SVR) decreased, but portal venous inflow (PVI) markedly increased (P<0.05). Seven or 15 days of L-NNA treatment reduced COX-1 mRNA expression in these vessels and the small intestine, concomitant with a significant decrease in the concentration of plasma PGI2 and serum NO in IHPH and PHPH rats (P<0.05). At the same time, PVI decreased but SVR increased significantly (P<0.05). In both IHPH and PHPH rats, the COX-1 mRNA expression and the concentration of plasma PGI2 after No synthase (NOS) blockade for 15 days were higher than those for 7 days, whereas the hyperdynamic circulatory state was improved after NOS blockade for 15 days compared with 7 days. The concentration of PGI2 treated by INDO for 15 days was not significantly different from that after 7-day COX blockade, and hemodynamics restored hyperdynamic circulatory state.
CONCLUSIONS: The hyperdynamic circulatory state in rats with PHT is correlated with the concentration of serum NO. There is a possible interaction between PGI2 and NO in the hyperhemodynamics of PHT. PGI2 is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT.
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Cite this article: |
Cao H,
Xu J,
Liu H,
et al.
Influence of nitric oxide synthase and cyclooxygenase blockade on expression of cyclooxygenase and hemodynamics in rats with portal hypertension.
Hepatobiliary Pancreat Dis Int
2006;
5(4):
564-569. DOI:
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URL: |
http://dx.doi.org/ OR http://www.hbpdint.com/EN/Y2006/V5/I4/564 |
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