Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function

• Published in: Frontiers in physiology 2020-11, Vol.11, p.593371-593371
• Main Authors: Caracuel, Laura, Sastre, Esther, Callejo, María, Rodrigues-Díez, Raquel, García-Redondo, Ana B, Prieto, Isabel, Nieto, Carlos, Salaices, Mercedes, Aller, Ma Ángeles, Arias, Jaime, Blanco-Rivero, Javier
• Format: Article
• Language: English
• Subjects: acute-on-chronic liver failure; bradykinin; cerebral vasculature; hepatic encephalopathy; nitric oxide; Physiology; prostaglandin I2
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2020.593371

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F releases were increased, whereas thromboxane (TX) B was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI synthase, and TXA S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE.