Simvastatin effects on portal-systemic collaterals of portal hypertensive rats

Hui Chun Huang, Sun Sang Wang, Jing Yi Lee, Yi Chou Chen, Fa Yauh Lee*, Han Chieh Lin, Ching Chih Chang, Shou Dong Lee


研究成果: Article同行評審

21 引文 斯高帕斯(Scopus)


Background and Aim: Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. Methods: Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from -2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM-0.1 μM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A2 synthase (TXA2-S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA2-S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1α and TXB2 levels were performed in parallel groups without AVP. Results: Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1α concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA2-S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness. Conclusion: Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities.

頁(從 - 到)1401-1409
期刊Journal of Gastroenterology and Hepatology (Australia)
出版狀態Published - 8月 2010


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