Altered endothelin receptor subtype expression in hepatic injury after ischemia/reperfusion

This study was performed to determine whether ischemia/reperfusion (I/R) in jury in rat liver results in alterations in endothelin receptor expression. Hepatic ischemia was produced in rats for 60 min followed by 6 or 24 h rep erfusion. Portal inflow pressure was increased (7.38 +/- 0.60 mmHg) at 24 h ours after reperfusion, Serum ALT increased significantly at both 6 and 24 h (6 h; 258.3 +/- 74.3, 24 h; 243.1 +/- 74.8 IU/L). Portal vascular respons e to an endothelin-B receptor agonist (IRL 1620) was significantly increase d in the I/R livers compared to control and this was potentiated by L-NAME, IRL 1620 also caused LDH release from I/R livers but not controls. LDH rel ease after IRL 1620 in I/R livers correlated with increased portal pressure response. To determine whether the altered response might be the result of altered endothelin receptor expression, livers were harvested after reperf usion and total endothelin binding sites were determined by competitive bin ding with ET-1. Proportion of endothelin receptor subtypes (ETA/ETB) was de termined using the ETA antagonist BQ-610 (1 mu M) and ETB agonist IRL-1620 (100 nM). There were no significant changes in Kd but Bmax for endothelin-1 was decreased in I/R group especially non-ischemic lobe at 24 h. ETA recep tors were significantly decreased whereas ETB receptors were increased. The se changes were more pronounced at 24 h after reperfusion than at 6 h. Inte restingly, the changes in ET receptors was observed identically both in isc hemic and non-ischemic lobes (ischemic lobe ETA 41.9%, ETB 51%, non-ischemi c robe ETA 38.8%, ETB 49.5%). These results indicate that the major functio nal endothelin receptor subtype upregulated in I/R is the ETB receptor and that this upregulation may contribute to microvascular dysregulation and he patic injury.