Immediate neuroendocrine signaling after partial hepatectomy through acute portal hyperpressure and cholestasis

• Published in: Journal of hepatology 2011-03, Vol.54 (3), p.481-488
• Main Authors: Doignon, Isabelle, Julien, Boris, Serrière-Lanneau, Valérie, Garcin, Isabelle, Alonso, Gérard, Nicou, Alexandra, Monnet, François, Gigou, Michelle, Humbert, Lydie, Rainteau, Dominique, Azoulay, Daniel, Castaing, Denis, Gillon, Marie-Christine, Samuel, Didier, Duclos-Vallée, Jean-Charles, Tordjmann, Thierry
• Format: Article
• Language: English
• Subjects: Adult; Animals; Arginine Vasopressin - physiology; Bile acids; Bile Acids and Salts - physiology; Biological and medical sciences; Blood Pressure - physiology; Chemical Sciences; Cholestasis; Cholestasis - physiopathology; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; GPBAR1; Hepatectomy; Humans; Hypertension, Portal - physiopathology; Liver Regeneration - physiology; Liver, biliary tract, pancreas, portal circulation, spleen; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; Neurosecretory Systems - physiology; Organic chemistry; Other diseases. Semiology; Portal pressure; Portal System - physiology; Rats; Rats, Wistar; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Signal Transduction; Supraoptic Nucleus - physiology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; TGR5; Vasopressin
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2010.07.012

Background & Aims Early neuroendocrine pathways contribute to liver regeneration after partial hepatectomy (PH). We investigated one of these pathways involving acute cholestasis, immediate portal hyperpressure, and arginine vasopressin (AVP) secretion. Methods Surgical procedure (PH, Portal vein stenosis (PVS), bile duct ligation (BDL), spinal cord lesion (SCL)) and treatments (capsaicin, bile acids (BA), oleanolic acid (OA)) were performed on rats and/or wild type or TGR5 (GPBAR1) knock-out mice. In these models, the activation of AVP-secreting supraoptic nuclei (SON) was analyzed, as well as plasma BA, AVP, and portal vein pressure (PVP). Plasma BA, AVP, and PVP were also determined in human living donors for liver transplantation. Results Acute cholestasis (mimicked by BDL or BA injection) as well as portal hyperpressure (mimicked by PVS) independently activated SON and AVP secretion. BA accumulated in the brain after PH or BDL, and TGR5 was expressed in SON. SON activation was mimicked by the TGR5 agonist OA and inhibited in TGR5 KO mice after BDL. An afferent nerve pathway also contributed to post-PH AVP secretion, as capsaicin treatment or SCL resulted in a weaker SON activation after PH. Conclusions After PH in rodents, acute cholestasis and portal hypertension, via the nervous and endocrine routes, stimulate the secretion of AVP that may protect the liver against shear stress and bile acids overload. Data in living donors suggest that this pathway may also operate in humans.