Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin

Abstract

Endothelin-1 (ET-1) acts on ET(A) and ET(B) receptors and has been implicated in hemorrhagic shock (shock). We determined effect of shock and resuscitation by hypertonic saline (saline) or centhaquin on ET(A) and ET(B) receptor expression. Rats were anesthetized, a pressure catheter was placed in the left femoral artery; blood was withdrawn from the right femoral artery to bring mean arterial pressure (MAP) to 35 mm Hg for 30 min, resuscitation was performed and 90 min later sacrificed to collect samples for biochemical estimations. Resuscitation with centhaquin decreased blood lactate and increased MAP. Protein levels of ET(A) or ET(B) receptor were unaltered in the brain, heart, lung and liver following shock or resuscitation. In the abdominal aorta, shock produced an increase (140 %) in ET(A) expression which was attenuated by saline and centhaquin; ET(B) expression was unaltered following shock but was increased (79 %) by centhaquin. In renal medulla, ET(A) expression was unaltered following shock, but was decreased (-61 %) by centhaquin; shock produced a decrease (-34 %) in ET(B) expression which was completely attenuated by centhaquin and not saline. Shock induced changes in ET(A) and ET(B) receptors in the aorta and renal medulla are reversed by centhaquin and may be contributing to its efficacy.