Expression of endothelin-1, and endothelin A and B receptors in portal hypertensive esophagus of rats

Nitric oxide synthase is overexpressed in the portal hypertensive (PHT) eso phagus, suggesting that expression of other vasoactive mediatora could also be affected. Therefore, in the present study we determined the expression of endothelin-1 (ET-1) and endothelin receptors, which could contribute to the regulation of the vascular tone in PHT esophagus. In esophageal specime ns of PHT and sham operated rats, expression of ET-1 and its receptors A an d B (ETAR and ETBR) mRNAs was studied by reverse transcription-polymerase c hain reactions. ET-1 protein expression was assessed by immunostaining and enzyme immunoassay. In PHT esophagus, expression of ET-1, ETAR and ETBR mRN As was significantly increased by 2.2-, 2.5- and 1.5-fold, respectively, co mpared with sham operated. The ET-1 protein was significantly increased by 2.2-fold vs. controls as measured by enzyme immunoassay. ET-1 protein was p redominantly localized to endothelia of submucosal veins. Thus, portal hype rtension induces over-expression of ET-1 in endothelia of esophageal submuc osal vessels. Since ET-1 and its receptors could promote vascular prolifera tion and induce mucosal damage, the overexpressed ET-1 may play an importan t role in the development and rupture of esophageal varices in portal hyper tension.