INHIBITION OF ENDOTHELIAL-DERIVED RELAXING FACTOR (EDRF) AGGRAVATES ISCHEMIC ACUTE-RENAL-FAILURE IN ANESTHETIZED RATS

The relative importance of endothelial derived relaxing factor (EDRF)/ nitric oxide (NO) in maintaining kidney function in normal condition a nd in acute renal failure (ARF) were evaluated in inactin anesthetized rats. ARF was induced by unilateral occlusion of the left renal arter y (40 min) followed by reperfusion, with the contralateral kidney serv ing as normal control. This protocol resulted in marked reductions in renal plasma flow (RPF), glomerular filtration rate (GFR) and increase s in fractional sodium excretion (FE(Na)) and urinary protein excretio n in the post-ischemic kidney in comparison to the contralateral norma l kidney. Administration of the nitric oxide (NO) synthase inhibitor N (G) - monomethyl-L-arginine (0.25 mg/kg, per, min, L-NMMA) exacerbated the ischemia-induced changes in renal functions as reflected by furth er reductions in urine flow (V), GFR, marked sodium wasting and renal edema. Pretreatment of the animals with NO precursor L-arginine (2.5 m g/kg per min, L-Arg) abolished the detrimental effects of L-NMMA in AR F. In contrast, D-Arginine (2.5 mg/kg per min, D-Arg) failed to revers e the detrimental effects of L-NMMA. Infusion of L-Arg alone also resu lted in improvements in RPF and GFR in the ischemic kidney. The result s of the present study suggest that the function of the ischemic kidne y is sustained by EDRF/NO and is thus more sensitive to NO synthase in hibition.