Acute effect of furosemide on endothelin-1 serum level and renal cortical oxygen tension

Introduction: Acute renal failure sometime appears while critically ill patients are on furosemide. The possible role of furosemide in the initiation of acute renal failure in these situations has never been evaluated. The purpose of this study was to evaluate the acute effect of furosemide on the renal cortical oxygen tension and endothelin-1 (Et-1) serum level in hypovolemic and hydration situations. Methods: Twenty-eight New Zealand White rabbits were anesthetized and mechanically ventilated. A carotid artery and internal jugular catheter were inserted for hemodynamic measurements. A tissue surface Clark-type electrode was placed at the surface of the left kidney for renal cortical oxygen tension measurements (PtO2). Hypovolemia was induced by peritoneal dialysis in fourteen rabbits. The others fourteen were hydrated with Lactated Ringer's at 30 ml/kg/hr. Furosemide or placebo was given in a randomized, blinded fashion in seven rabbits of both situations. PtO2 and Et-1, measured by enzymoimmunoassay (Peninsula Laboratories Inc), were measured before and after 3h of drug exposure. Results: Furosemide did not change Et-1 or PtO2 significantly when compared to the either control group, Et-1 levels were unchanged in both the hydration groups (32 ± 19 to 36 ± 15 ng/ml at 3h) and in the hypovolemic groups (39 ± 19 to 47 ± 13 ng/ml at 3h). However, there was a trend to lower cortical PO2 (from 53 ± 18 torr at baseline to 44 ± 29 torr at 3h) along with lower mean arterial blood pressure (from 56 ± 16 torr to 42 ± 11 torr) after furosemide but not after placebo in the hypovolemic situation. Conclusion: In this study, furosemide did not appear to have any major effect on Et-1 levels or cortical oxygen tension after 3 hours. However, as expected, furosemide has an indirect effect on cortical blood flow in the hypovolemic rabbit as indicated by its effect on the cortical PO2 and may be an indirect contributor to acute renal failure in the already hypovolemic subject. Further studies detailing histopathological changes are necessary.