Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction

• DOI: 10.1002/hep.26127
• Publication Date: 2012-11-26T20:50:50Z
• Authors: Vincenzo La Mura; Marcos Pasarín; Cintia Z. Meireles; Rosa Miquel; Aina Rodríguez-Vi...; Diana Hide; Jorge Gracia-Sancho; Juan Carlos Garcí...; Jaime Bosch; Juan G. Abraldes
• Keywords: Endothelial Dysfunction

Endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are largely unknown. Statins might improve microvascular in The present study explores abnormalities effects statins a rat model endotoxemia. For this purpose, lipopolysaccharide (LPS) or saline was given to: (1) rats treated placebo; (2) simvastatin (25 mg/kg, orally), at 3 23 hours after LPS/saline challenge; (3) mg/kg/24 h, orally) from days before injection. Livers were isolated perfused explored by testing vasodilation circulation to increasing concentrations acetylcholine. phosphorylated nitric oxide synthase (PeNOS) / (eNOS) ratio measured as marker eNOS activation. LPS administration induced an increase baseline portal perfusion pressure decrease acetylcholine (sinusoidal dysfunction). This reduced phosphorylation inflammation. Simvastatin challenge did not prevent pressure, but attenuated development dysfunction. Treatment prevented totally normalized vasodilating response vasculature Both protocols treatment restored physiologic PeNOS/eNOS ratio. Conclusion: induces intrahepatic that be simvastatin, suggesting have potential for protection during (Hepatology 2013)