title: Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats.
abstract: OBJECTIVE
  To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.
  
  
  METHODS
  Glytan (Ganluotong in Chinese), is composed of salvianolic acid B and diammonium glycyrrhizinate. Portal hypertension (PHT) was induced in the rats by common bile duct ligation (BDL). Hemodynamic studies were performed using the colored microsphere method. Radioimmunoassay (RIA) was used to determine endothelin (ET)-1 levels in the mesenteric circulation. Western blotting methods were used to investigate the effect of Glytan on ET A receptor (ETAR), ET B receptor (ETBR), endothelial NO synthase (eNOS), G-protein-coupled receptor kinase (GRK)2, and β-arrestin 2 expression in the mesentery. The mRNA of ETAR and ETBR was determined using real-time polymerase chain reaction.
  
  
  RESULTS
  Treatment with Glytan reduced portal pressure (PP) and portal territory blood flow (PTBF) and increased both mean arterial pressure (MAP) and splanchnic vascular resistance (SVR). Especially at 4 wk, PP decreased by about 40%, while MAP increased by 13%, SVR increased by 12%, and PTBF decreased by about 21%. The effect of blood flow reduction was greatest in the mesentery (about 33%) at 4 wk. The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk. Glytan can increase mesenteric ET-1 content and inhibit ETBR, eNOS, GRK2, and β-arrestin 2 expression in the mesentery. Moreover, Glytan showed no effect on the expression of ETAR protein and mRNA.
  
  
  CONCLUSIONS
  The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Qing-Hong
authors.initials: QH
authors.lastname: Du
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Jiang
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Li
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Peng-Tao
authors.initials: PT
authors.lastname: Li
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jia
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D065131:Endothelin B Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000097:blood; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006975:Hypertension, Portal / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D017082:Portal Pressure / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D047428:Protein Kinase Inhibitors; D044023:Receptor, Endothelin B; D014662:Vasoconstrictor Agents; C000600391:ganluotong; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D006034:Glycyrrhetinic Acid
keywords: Endothelin-1; Glytan; Hemodynamics; Mesentery; Portal hypertension; Receptor; Sensitivity