Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats.
Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Merck, Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
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D058186:Acute Kidney Injury / Q000378:metabolism*; D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005990:Glycerol; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D014501:Uranium; D014502:Uranyl Nitrate; D014511:Uremia / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D013757:Tetraethylammonium Compounds; D014502:Uranyl Nitrate; D014501:Uranium; D019789:Tetraethylammonium; D005990:Glycerol; D010130:p-Aminohippuric Acid