Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2014; 20(44): 16674-16682
Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16674
Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats
Qing-Hong Du, Lin Han, Jun-Jie Jiang, Ya Xu, Wei-Hong Li, Peng-Tao Li, Xin-Yue Wang, Xu Jia
Qing-Hong Du, Lin Han, Ya Xu, Wei-Hong Li, Xu Jia, School of Fundamental Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Jun-Jie Jiang, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
Peng-Tao Li, Xin-Yue Wang, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
Author contributions: Du QH and Han L contributed equally to this work and are co-first authors in this study; Du QH, Han L, Li PT and Li WH designed the research; Du QH, Han L, Jiang JJ, Xu Y and Jia X performed the research; Wang XY contributed new analytic tools; Du QH, Han L and Li WH analyzed the data; and Du QH and Han L wrote the paper.
Supported by Grants from National Key New Drug Creation Project of China, No. 2009ZX09102; and National Natural Science Foundation of China, No. 81273885
Correspondence to: Wei-Hong Li, MD, School of Fundamental Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China. liweihong.403@163.com
Telephone: +86-10-64286526
Received: February 17, 2014
Revised: April 18, 2014
Accepted: May 25, 2014
Published online: November 28, 2014
Abstract

AIM: 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.

CONCLUSION: The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.

Keywords: Glytan, Portal hypertension, Hemodynamics, Mesentery, Endothelin-1, Receptor, Sensitivity

Core tip: The traditional Chinese medicine Glytan is composed of salvianolic acid B and diammonium glycyrrhizinate. Previous studies have shown that Glytan is a new preparation for portal hypertension. The present study indicated that decreases in portal pressure and portal territory blood flow observed after Glytan treatment in portal hypertensive rats were related to increased mesenteric endothelin-1 content and reduced endothelin B receptor, endothelial NO synthase, G-protein-coupled receptor kinase 2, and β-arrestin 2 expression, which may promote mesenteric vasoconstriction and increase receptor sensitivity to vasoconstrictors. These results suggest the therapeutic potential of Glytan in portal hypertension induced by liver cirrhosis.