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Preventive strategies in endothelin-induced renal failure
M Hermann1, E Schulz, F Ruschitzka
1Department of Nephrology/Rheumatology, Center of Internal Medicine, University of Göttingen, Germany.
Kidney International. Supplement
|September 15, 1998
Summary
Endothelin (ET) causes acute kidney injury when fibrinolysis and prostanoids are blocked. Hirudin, an anticoagulant, provided the most protection against ET-induced renal dysfunction in pigs, suggesting a key role for thrombin in ET
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Physiology
Background:
- Endothelin (ET) is a potent vasoconstrictor that can induce acute renal failure.
- Inhibition of fibrinolysis and prostanoids exacerbates ET-induced renal damage.
- Understanding protective mechanisms against ET toxicity is crucial for managing acute kidney injury.
Purpose of the Study:
- To compare the efficacy of nifedipine, hirudin, and enalapril in preventing endothelin-induced acute renal failure in a porcine model.
- To investigate the effects of these therapeutic agents on coagulation, prostanoid synthesis, and renal function.
- To elucidate the pathways involved in endothelin's hemodynamic and renal effects.
Main Methods:
- Anesthetized female pigs were pretreated with indomethacin and epsilon-aminocaproic acid to inhibit prostanoids and fibrinolysis.
- Four endothelin boli were administered to control animals or animals additionally treated with nifedipine, hirudin, or enalapril.
- Parameters assessed included blood pressure, prostanoid levels, coagulation markers, and renal function (creatinine clearance).
Main Results:
- Endothelin-induced hypertension was significantly attenuated by nifedipine, hirudin, and enalapril, with hirudin showing the greatest effect.
- Prostanoid synthesis was blocked in all groups.
- Hirudin effectively prevented disseminated intravascular coagulation, while nifedipine and enalapril attenuated it. Renal function recovery was most pronounced in the hirudin group.
Conclusions:
- All tested therapeutic agents demonstrated protective effects against endothelin-induced renal dysfunction.
- Hirudin emerged as the most potent protective agent, potentially by preventing ET-mediated thrombin release.
- These findings highlight critical pathways mediating endothelin's cardiovascular and renal effects, with implications for acute kidney injury treatment.