Preventive strategies in endothelin-induced renal failure.
The endothelial vasoconstrictor endothelin (ET) can induce acute renal failure when fibrinolysis and vasodilatory prostanoids (PGs) are inhibited. This study compares therapeutic agents preventing ET-induced acute renal failure in anesthetized female pigs. We investigated the effect of four ET boli (1.5 microg/kg, i.v.) after pretreatment with indomethacin (2 mg/kg) and epsilon-aminocaproicacid (100 + 50 mg/kg) alone (controls, group 1) or during additional nifedipine (10 microg/kg/h; group 2), hirudin (0.5 mg/kg; group 3), or enalapril (2 x 0.15 mg; group 4) on coagulation, PGs, and renal function. The ET-induced blood pressure increase was lower in groups 2 to 4 (lowest in group 3, P < 0.05). PG synthesis was blocked in all groups. The initial hypercoagulability (controls) resulted in disseminated intravascular coagulation that was prevented by hirudin and was attenuated in groups 2 and 4. At the end of the experiment, creatinine clearance was significantly (P < 0.05) decreased. The recovery of renal function two hours after the last ET bolus was most pronounced in the hirudin group. All therapeutic drugs attenuated ET-induced impairment of renal function. Hirudin seems to be the most potent protective drug. Prevention of further ET release evoked by ET-mediated secretion of thrombin might explain this. These results suggest three important pathways for ET's hemodynamic and renal effects.
Hermann
M
M
Department of Nephrology/Rheumatology, Center of Internal Medicine, University of Göttingen, Germany.
Schulz
E
E
Ruschitzka
F
F
Müller
G A
GA
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D016232:Endothelins; D005260:Female; D006629:Hirudins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D013552:Swine; D014662:Vasoconstrictor Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000991:Antithrombins; D002121:Calcium Channel Blockers; D016232:Endothelins; D006629:Hirudins; D014662:Vasoconstrictor Agents; D004656:Enalapril; D003404:Creatinine; D009543:Nifedipine; D007213:Indomethacin