Terutroban, a TP receptor antagonist, restores renal artery tone, but not renal function in mouse with 5/6 nephrectomy

Aim Thromboxane A2（TXA2） is assumed to contribute to the process of renal dysfunction. The pres- ent study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglandin？ （TP） receptor, protects against renal damage in 5/6 nephrectomy. Methods C57/BL6 mice were randomly grouped into sham-operated （2K）, 5/6 nephroectomy groups （5/6K-off） and 5/6 nephroectomy treated with ter- utroban （10 mg · kg^-1 · d^-l） groups （Yerutroban）. Renal artery and kidney were collected for vascular function study, Western blot, immunohistochemistry （IHC） assay and enzyme-linked immunosorbent assay （ELISA）, re- spectively. Results Four weeks after the surgery, arterial blood pressure was comparable among the three groups. However mice in terutroban group had higher levels of serum creatinine and lower survival. Compared with 2K groups, 5/6K-off mice had significantly higher levels of renal blood flow as well as a blunted relaxation to acetyl- choline. Production of prostacyclin （PGI2） and thromboxane B2 （ TXB2）, but no prostaglandin E2 （ PGE2）, were significantly increased in the renal artery of 5/6K-off group. Terutroban restored the renal blood flow, but not the acetylcholine-induced relaxation in the renal artery. It is probably due to the blockade effect of terutroban on the smooth muscle since terutroban treatment significantly reduced U46619-induced vasconstriction in renal arteries. Interestingly, terutroban increased the production of TXB2, but not PGI2 or PGE2, in the renal artery. This proba-bly is a compensatory effect on prostaglandins production. In kidney cortex, 5/6K-off group had significantly lower levels of PGE2 and TXB2 when compared with 2 K group. Terutroban markedly increased all three prostaglandins levels. Conclusion Terutroban restores renal artery function, but not renal function in mouse with 5/6 nephrecto- my. It suggests that kidney has more complicated regulations than renal artery. High levels of prostanoids in kid- neys may contribute to renal damage in terutroban group. Further experiments will focus on examining the underly- ing mechanisms.