Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis

Hepatology. 2000 May;31(5):1107-14. doi: 10.1053/he.2000.6596.


This study was aimed to evaluate the source of endothelin-1 (ET-1) in cirrhotic patients. ET-1 is implicated in the pathogenesis of portal hypertension. However, the mechanism and source for increased plasma ET-1 in cirrhotic patients are still obscure. Plasma ET-1 levels in systemic (SV), superior mesenteric (SMV), and splenic venous (SPV) blood were measured in 23 patients with cirrhosis and 8 controls with normal liver. Fourteen removed spleens were immunohistochemically studied for ET-1, CD34, CD68, and CD20. In situ hybridization was done to localize ET-1 messenger RNA (mRNA). In cirrhosis, ET-1 levels in both SMV and SPV were higher than in SV. ET-1 in SV and SPV were significantly higher in cirrhotic patients than in control patients. Three groups of cells in the spleen expressed both protein and mRNA of ET-1: endothelial cells in the sinus, which were also stained for CD34; cells in the germinal center; and cells in the marginal zone of lymphoid sheaths and follicles, which were also stained for CD20 but not for CD34 and CD68. The ET-1 concentration released from the spleen was in parallel with the grade of ET-1 expression in the spleen. The spleen is one of the major sites of ET-1 release in cirrhotic patients. Endothelial cells of the splenic sinus and possibly B lymphocytes in the germinal center and marginal zone of lymphoid sheaths and follicles seem to be the sites of ET-1 production in the spleen.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Female
  • Humans
  • Hypertension, Portal / metabolism*
  • In Situ Hybridization
  • Intestinal Mucosa / metabolism*
  • Liver Cirrhosis / complications*
  • Male
  • Middle Aged
  • Portal Vein / physiopathology
  • Spleen / metabolism*
  • Venous Pressure


  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Endothelin-1