Endothelin-1 Acutely Reduces the Permeability of Visceral Sheep Peritoneum In Vitro Through Both Endothelin-A and Endothelin-B Receptors

Abstract

Mesothelium is an important part of the peritoneal barrier for water and ion transport, essential for effective peritoneal dialysis (PD). Peritoneal fibrosis has been associated with PD treatment failure. Endothelin-1 (ET-1) is a potent vasoactive peptide, involved in pathologic fibrotic processes. Its action is mediated mainly by endothelin type A (ETA) and type B (ETB) receptors. The aim of this study was to investigate, by Ussing chamber experiments, the effect of ET-1 on the transmesothelial electrical resistance (RTM) of the isolated visceral sheep peritoneum. Intact sheets of visceral peritoneum were obtained from 40 adult sheep and mounted in Ussing-type chambers. ET-1 (107M), BQ-123 (ETA receptor antagonist; 106M), BQ-788 (ETB receptor antagonist; 106M), and their combinations were added on the apical and the basolateral side of the peritoneum. RTM was measured before and serially after addition of the substances, and changes were registered as percentage (RTM %). RTM increased within 1min after addition of ET-1 apically (RTM 65.03 +/- 15.87%; P<0.05) or basolaterally (RTM 85.5 +/- 20.86%; P<0.05). BQ-123 and BQ-788 and their combination significantly reduced (P<0.05) the effect of ET-1 to a similar degree in all cases. These results clearly indicate that ET-1 reduces ionic permeability of the visceral sheep peritoneum in vitro. Additionally, it is obvious that this inhibitory effect is mediated through both ETA and ETB receptors.