Selective cyclooxygenase-1 inhibition improves collateral vascular reactivity in biliary cirrhotic rats

Ching Chih Chang, Chiao Lin Chuang, Wen Shin Lee, Sun Sang Wang, Fa Yauh Lee*, Han Chieh Lin, Hui Chun Huang, Shou Dong Lee


研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)


Background: Evidence has demonstrated that overproduction of prostacyclin (PGI2) is critical in the pathogenesis of splanchnic hyposensitivity to vasoconstrictors in the cirrhotic state. The biosynthesis of PGI2 is through cyclooxygenase (COX). This study evaluated which isoform of COX is dominant in the mechanism of collateral vascular reactivity of biliary cirrhotic rats. Methods: Three groups of formalin-injected common bile duct-ligated (FBDL) induced cirrhotic rats received two doses of: (1) selective COX-1 inhibitor (SC-560 2mg/kg); (2) COX-2 inhibitor (NS-398 2mg/kg); (3) dimethyl sulfoxide (control). Subsequently, the rats were kept in metabolic cages for 24 hours to collect urine. Thereafter, the systemic and portal hemodynamics and renal function were measured. In another series, using in-situ collateral perfusion model, the collateral vascular responses to arginine vasopressin (AVP) were measured in the subject rats after preincubation of vehicle (Krebs solution), SC-560 (5μM) or NS-398 (10μM). Results: The mean arterial pressure, heart rate, and portal pressure were similar among SC-560-treated, NS-398-treated, and control groups. Additionally, there was no significant difference in the calculated creatinine clearance rates among these three groups. SC-560 preincubation significantly enhanced the pressor effect of AVP at the concentration of 3M×10-9M (11.0±1.0mmHg vs. 6.4±0.6mmHg, p=0.002) in the cirrhotic rats. Conclusion: There was no significant hemodynamic change and renal toxicity after acute administration of COX inhibitor in the FBDL-induced cirrhotic rats. Preincubation of selective COX-1, but not COX-2, inhibitor could enhance collateral vascular response to AVP, indicating that COX-1 plays a major role in the collateral vascular reactivity.

頁(從 - 到)557-563
期刊Journal of the Chinese Medical Association
出版狀態Published - 10月 2013


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