Abstract
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-κB).
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-κB was significantly increased (P<0.01) in comparison with the sham operation group. All of these changes were significantly reversed after CPU0213 administration.
Conclusion:
Upregulation of the ET signaling pathway and NF-κB play an important role in the ARF of septic shock. Amelioration of renal lesions was achieved by suppressing the ETA and ETB receptors in the renal cortex following CPU0213 medication.
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Project supported by the National Natural Science Foundation of China (No 30230170 and No 30572193).
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He, Hb., Dai, Dz. & Dai, Y. CPU0213, a novel endothelin receptor antagonist, ameliorates septic renal lesion by suppressing ET system and NF-κB in rats. Acta Pharmacol Sin 27, 1213–1221 (2006). https://doi.org/10.1111/j.1745-7254.2006.00373.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00373.x
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