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Acta Pharmacologica Sinica 2006 September; 27 (9): 1213-1221; doi: 10.1111/j.1745-7254.2006.00373.x |
| Original Article | [ Full text ] |
| CPU0213, a novel endothelin receptor antagonist, ameliorates septic renal lesion by suppressing ET system and NF-kB in rats |
Hai-bo HE, De-zai DAI2, Yin DAI Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China |
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Aim: To examine whether a novel endothelin receptor antagonist, CPU0213, is effective in relieving the acute renal failure (ARF) of septic shock by suppressing the activated endothelin-reactive oxygen species (ET-ROS) pathway and nuclear factor kappa B (NF-kB).
Methods: The cecum was ligated and punctured in rats under anesthesia. CPU0213 (30 mg·kg-1·d-1, bid, sc×3 d) was administered 8 h after surgical operation.
Results: In the untreated septic shock group, the mean arterial pressure and survival rate were markedly decreased (P<0.01), and heart rate, weight index of kidney, serum creatinine and blood urea nitrogen, 24 h urinary protein and creatinine were significantly increased (P<0.01). The levels of ET-1, total NO synthetase (tNOS), indusible nitric oxide synthetase (iNOS), nitric oxide (NO), and ROS in serum and the renal cortex were markedly increased (P< 0.01). The upregulation of the mRNA levels of preproET-1, endothelin converting enzyme, ETA, ETB, iNOS, and tumor necrosis factor-alpha in the renal cortex was significant (P<0.01). The protein amount of activated NF-kB was significantly increased (P<0.01) in comparison with the sham operation group. All of these changes were significantly reversed after CPU0213 administration.
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Keywords: septic shock; acute renal failure; endothelin receptor antagonist; NF-kB; reactive oxygen species |
| 1 Project supported by the National Natural Science Foundation of China (No 30230170 and No 30572193). |
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