We studied whether endothelin-1 (ET-1) and its receptor subtypes (ETAR, endothelin A type receptor; and ETBR, B type receptor) were up-regulated in the glomerulus of a rat model of mesangial proliferative glomerulonephritis induced by anti-thymocyte serum (anti-Thy-1 GN). A marked increase in preproET-1 mRNA could be demonstrated in glomerular RNA 3 and six days after disease induction (4.1- and 4.9-fold vs. day 0, respectively), corresponding to the time of mesangial cell proliferation, to the time of macrophage infiltration into glomeruli, and also to the time of increase in glomerular PDGF B-chain mRNA expression. The localization of ET-1 protein in the mesangial area and along the inner aspect of the glomerular capillary wall was also demonstrated by immunohistochemistry from day 3 and maximal at day 6. The major source of the cells expressing ET-1 in glomeruli appeared to be mesangial cells, glomerular endothelial cells and monocyte/macrophages. Furthermore, both gene and protein expression of ET-1 were associated with increased urinary excretion of ET-1. There was no increase in the plasma ET-1 immunoreactivity. Glomerular expression of ETBR mRNA increased in anti-Thy-1 GN (1.5-fold vs. day 0 at day 3 after disease induction, 3.6-fold at day 6 and 2.7-fold at day 10), but there was minimal change in ETAR mRNA expression. These results suggest that preproET-1 mRNA, which is induced in anti-Thy-1 GN, is linked primarily with ETBR mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)