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Influence of nitric oxide synthase and cyclooxygenase blockade on expression of cyclooxygenase and hemodynamics in rats with portal hypertension.
Hepatobiliary Pancreat Dis Int. 2006 Nov; 5(4):564-9.HP

Abstract

BACKGROUND

The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI(2)) 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 (PGI(2)) 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 N(omega)-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 CCl(4), 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 (NO(2)(-)/NO(3)(-), micromol/L) by a colorometric method, and that of PGI(2) was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF(1alpha) (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-PGF(1alpha) and serum NO(2)(-)/NO(3)(-) 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 PGI(2) 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 PGI(2) 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 PGI(2) 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 PGI(2) and NO in the hyperhemodynamics of PHT. PGI(2) is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT.

Authors+Show Affiliations

Department of Surgery, Renji Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200127, China. xujia201800@126.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17085343

Citation

Cao, Hui, et al. "Influence of Nitric Oxide Synthase and Cyclooxygenase Blockade On Expression of Cyclooxygenase and Hemodynamics in Rats With Portal Hypertension." Hepatobiliary & Pancreatic Diseases International : HBPD INT, vol. 5, no. 4, 2006, pp. 564-9.
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. HBPD INT. 2006;5(4):564-9.
Cao, H., Xu, J., Liu, H., Meng, F. B., Qiu, J. F., & Wu, Z. Y. (2006). Influence of nitric oxide synthase and cyclooxygenase blockade on expression of cyclooxygenase and hemodynamics in rats with portal hypertension. Hepatobiliary & Pancreatic Diseases International : HBPD INT, 5(4), 564-9.
Cao H, et al. Influence of Nitric Oxide Synthase and Cyclooxygenase Blockade On Expression of Cyclooxygenase and Hemodynamics in Rats With Portal Hypertension. HBPD INT. 2006;5(4):564-9. PubMed PMID: 17085343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of nitric oxide synthase and cyclooxygenase blockade on expression of cyclooxygenase and hemodynamics in rats with portal hypertension. AU - Cao,Hui, AU - Xu,Jia, AU - Liu,Hua, AU - Meng,Fang-Bin, AU - Qiu,Jiang-Feng, AU - Wu,Zhi-Yong, PY - 2006/11/7/pubmed PY - 2007/2/9/medline PY - 2006/11/7/entrez SP - 564 EP - 9 JF - Hepatobiliary & pancreatic diseases international : HBPD INT JO - HBPD INT VL - 5 IS - 4 N2 - BACKGROUND: The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI(2)) 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 (PGI(2)) 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 N(omega)-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 CCl(4), 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 (NO(2)(-)/NO(3)(-), micromol/L) by a colorometric method, and that of PGI(2) was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF(1alpha) (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-PGF(1alpha) and serum NO(2)(-)/NO(3)(-) 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 PGI(2) 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 PGI(2) 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 PGI(2) 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 PGI(2) and NO in the hyperhemodynamics of PHT. PGI(2) is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT. SN - 1499-3872 UR - https://www.unboundmedicine.com/medline/citation/17085343/Influence_of_nitric_oxide_synthase_and_cyclooxygenase_blockade_on_expression_of_cyclooxygenase_and_hemodynamics_in_rats_with_portal_hypertension_ DB - PRIME DP - Unbound Medicine ER -