Oxygen free radical mediated renal dysfunction.
Postischemic renal dysfunction (PIRD) is characterized by a reduction in glomerular filtration and tubular reabsorption of solute. The relative contribution of oxygen free radicals (OFRs) generated during reperfusion remains unclear. This study characterized the renal response to OFRs--independent of an ischemic insult. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with a modified Krebs' buffer. Hypoxanthine (25 mumole) and xanthine oxidase (1 unit) were combined and infused proximal to the kidney. There was a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and a 70% reduction in glomerular filtration rate. There was also a significant reduction in urine flow rate and oxygen consumption. The percentage reabsorption of filtered water and sodium by the renal tubules was not diminished, however. This pattern was not observed when the xanthine oxidase was inactivated or when the perfusate was pretreated with superoxide dismutase (250 units/ml) and catalase (500 units/ml). The generation of OFRs, independent of an ischemic insult, causes a decrease in glomerular filtration out of proportion to the decrease in renal flow similar to that observed with PIRD. OFRs may contribute to the hemodynamic and glomerular alterations seen with PIRD. Factors other than OFRs, probably associated with ischemia, must be responsible for the tubular dysfunction.
Galat
J A
JA
Department of Surgery, Case Western Reserve University, Cleveland, Ohio 44106.
Robinson
A V
AV
Rhodes
R S
RS
D000818:Animals; D005609:Free Radicals; D005919:Glomerular Filtration Rate; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000008:administration & dosage; D014554:Urination; D014655:Vascular Resistance; D014969:Xanthine Oxidase / Q000008:administration & dosage / Q000494:pharmacology*
D005609:Free Radicals; D007042:Hypoxanthines; D019271:Hypoxanthine; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase