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

This study was aimed to evaluate the source of endothelin-1 (ET-1) in cirrh otic patients. ET-1 is implicated in the pathogenesis of portal hypertensio n. 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 patien ts with cirrhosis and 8 controls with normal liver. Fourteen removed spleen s were immunohistochemically studied for ET-1, CD34, CD68, and CD20. In sit u hybridization was done to localize ET-1 messenger RNA (mRNA). In cirrhosi s, ET-1 levels in both SMV and SPV were higher than in SV; ET-1 in SV and S PV 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 Ca20 but not for CD34 and CD68. The ET-1 concentration released from the spleen was in parallel with the g rade 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 si nus 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 t he spleen.