Functional basis for the glomerular alterations in uranyl nitrate acute renal failure.
We have examined the acute renal failure that occurs after uranyl nitrate administration in the rat and the specific effects of pretreatment of rats with angiotensin converting enzyme inhibitor (CEI), plasma volume expansion (PVE) after uranyl nitrate, and a combination of these treatments. We utilized a combination of micropuncture measurements of glomerular hemodynamics, cage studies, and histologic examination of renal tissue to evaluate the degree of acute renal failure in all groups studied. Uranyl nitrate (UN) (25 mg/kg body wt) administration caused a reduction in the nephron filtration rate (SNGFR) (39.4 +/- 1.6 to 24.8 +/- 2.9 nl X min-1 X g kidney wt-1, P less than 0.02) as a result of a major decrease in the glomerular ultrafiltration coefficient (LpA) from control values (greater than or equal to 0.085 +/- 0.008 to 0.035 +/- 0.007 nl X sec-1 X mm Hg-1 X g kidney wt-1, P less than 0.01). Treatments with CEI, PVE, and the combination of CEI and PVE in rats receiving UN restored 0.38 +/- LpA to normal values (greater than 0.061 +/- 0.009, 0.091 +/- 0.020, and 0.138 +/- 0.020 nl X sec-1 X mm Hg-1 X g kidney wt-1, respectively). Cage studies revealed that CEI treatment prevented oliguria and resulted in major volume losses and reduction in weight. However, rats died after a similar period after UN, but probably by different mechanisms. Analysis of renal ultrastructure revealed equivalent tubular damage in all experimental groups. Alterations in LpA after UN are functional in nature and are potentially preventable and reversible by a combination of treatments with CEI and PVE.
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D003681:Dehydration / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000494:pharmacology; D009929:Organ Size; D010953:Plasma Volume; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide; D014501:Uranium; D014502:Uranyl Nitrate; D014556:Urine
D009842:Oligopeptides; D014502:Uranyl Nitrate; D014501:Uranium; D013722:Teprotide