The mesothelium is part of the peritoneal barrier that manages the water and ion transport essential for peritoneal dialysis (PD) treatment. In addition, it has a central role in the pathogenesis of peritoneal fibrosis and the resulting ultrafiltration failure observed in many PD patients. Endothelin-1 (ET-1) is a potent vasoactive peptide originally described as an endothelial cell-derived factor In addition, ET-1 has been shown to stimulate fibrogenic activity in various organs by regulating the production and turnover of matrix components. The aim of the present study was to investigate, by means of Ussing chamber experiments, the effect of ET-1 on the transmesothelial electrical resistance (RTM) of isolated visceral sheep peritoneum. Intact sheets of visceral sheep peritoneum were obtained from 12 adult sheep. The samples were collected from the slaughterhouse immediately after the deaths of the animals and, within 30 minutes, were transferred in oxygenated Krebs-Ringer bicarbonate (KRB) solution at 4 degrees C to the laboratory to be mounted in an Ussing-type chamber. Endothelin-1 (10(-7) mol/L) was then added to the KRB solution apically or basolaterally, and the RTM was measured before and serially for 10 minutes after the addition of the ET-1. The control RTM (before addition of ET-1) was 22.8 +/- 0.56 Omega x cm2. Addition of ET-1 apically significantly increased the RTM by 63.82% +/- 16.93% (p < 0.05) within 1 minute. After addition of ET-1 basolaterally, the RTM also increased significantly by 90.91% +/- 57.31% within 1 minute (p < 0.05). In both cases, these values persisted throughout the experiment. These results clearly indicate an inhibitory effect of ET-1 on the ionic permeability of visceral sheep peritoneum. The rapid increase in RTM observed after the addition of ET-1 suggests the existence of endothelin receptors (ET-A or ET-B, or both) on visceral sheep peritoneum. Previous studies demonstrated that ET-1, acting on ET-B receptors, potently inhibits epithelial sodium channels in mammalian cell cultures. Nevertheless, the exact pathways that underlie these findings remain unclear; their elucidation requires further investigation.