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Simvastatin effects on portal-systemic collaterals of portal hypertensive rats.
MedLine Citation:
PMID:  20659230     Owner:  NLM     Status:  In-Process    
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 microM) 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 A(2) synthase (TXA(2)-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 TXA(2)-S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1(alpha) and TXB(2) levels were performed in parallel groups without AVP. RESULTS: Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1(alpha) concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA(2)-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.
Hui-Chun Huang; Sun-Sang Wang; Jing-Yi Lee; Yi-Chou Chen; Fa-Yauh Lee; Han-Chieh Lin; Ching-Chih Chang; Shou-Dong Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  25     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1401-9     Citation Subset:  IM    
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
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