The Effects of Endothelin Receptor Antagonist Bosentan on Diabetic Rats

Objective:To investigate the effects of endothelin receptor antagonist Bosentan on the endothelin system in diabetic SD rat.Methods:SD rats were divided into 3 groups at random: untreated diabetic group (DM), Bosentan treated diabetic group (DM-B) and normal control group (SD). Diabetic rats were induced by one dose intraperitoneal injection of Streptozotocin. The DM-B group was treated with Bosentan 100 mg·kg -1 ·d -1 through stomach perfusion for 4 weeks, while the DM and SD groups were treated with sterile water only. The concentrations of circulating and renal endothelin in 3 rats groups were then detected. Furthermore, the kidney expressions of endothelin-1(ET-1), endothelin A receptor (ET-AR) and endothelin B receptor (ET-BR) were measured by reverse transcription-polymerase chain reaction and immuno-histochemistry.Results:There are only a few expressions of ET-1, ET-AR and ET-BR in SD rats kidneys. Elevated level of renal ET-1 was observed in two diabetic groups through RT-PCR ( P 0.01 vs SD group) and no significant difference between the two groups were observed. Notable more renal expressions of ETAR were detected in DM compared with SD group. Bosentan can decrease the elevated of ET-AR expressions( P 0.01 vs DM group). However, there is no significant difference of ET-BR expressions in the three groups.Conclusion:Endothelin has a high activity in diabetic rats. Bosentan can not only interfere with the effects of ET-1, but also down-regulate the elevated renal expressions of ETAR in diabetic rats, so it is useful in keeping kidney from injury in diabetes mellitus.