Related Experiment Videos
Bosentan, an orally active endothelin antagonist: effect on the renal response to contrast media
S D Oldroyd1, J L Haylor, S K Morcos
1Sheffield Kidney Institute, Northern General Hospital, Sheffield, England.
Purpose:
To examine the effect of bosentan, an orally active endothelin-receptor antagonist, on the renal response to contrast media in the isolated perfused rat kidney (IPRK) and to establish whether bosentan can inhibit contrast media-induced nephrotoxicity in a multiple-insult model in the conscious rat.
Materials And Methods:
Renal function was measured in the IPRK (n = 24) and in the rats that had undergone unilateral nephrectomy, were maintained on a salt-free diet, and were receiving indomethacin (10 mg/kg/d; n = 60).
Results:
In the IPRK, diatrizoate and iotrolan reduced the glomerular filtration rate and renal perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In the multiple-insult rat model, the fall in creatinine clearance produced by diatrizoate was also markedly inhibited by bosentan (n = 15 per group).
Conclusion:
Endothelin antagonists such as bosentan may be used to reduce the prevalence of contrast-induced nephrotoxicity.
Insights
Bosentan, an endothelin-receptor antagonist, protected rat kidneys from contrast media-induced damage in both isolated perfused kidney and conscious rat models. This suggests endothelin antagonists may prevent contrast-induced nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Renal Physiology
Background:
- Contrast media administration can lead to contrast-induced nephrotoxicity.
- Endothelin plays a role in regulating renal blood flow and function.
Purpose of the Study:
- To investigate the protective effects of bosentan, an endothelin-receptor antagonist, against contrast media-induced renal injury.
- To evaluate bosentan's efficacy in preventing nephrotoxicity in both an isolated perfused rat kidney model and a multiple-insult conscious rat model.
Main Methods:
- Utilized an isolated perfused rat kidney (IPRK) model to assess renal function and blood flow.
- Employed a multiple-insult model in conscious rats (unilateral nephrectomy, salt-free diet, indomethacin) to evaluate creatinine clearance after contrast media exposure.
Main Results:
- In the IPRK, bosentan significantly inhibited the reduction in glomerular filtration rate and renal perfusate flow caused by contrast media (diatrizoate and iotrolan).
- In conscious rats, bosentan markedly attenuated the decrease in creatinine clearance induced by diatrizoate exposure.
Conclusions:
- Endothelin receptor antagonists, such as bosentan, demonstrate potential in mitigating contrast media-induced nephrotoxicity.
- These findings suggest a therapeutic role for endothelin antagonists in preventing kidney damage associated with contrast media administration.