Urinary excretion and tissue accumulation of gentamicin and paraaminohippurate in postischemic rat kidneys.
Unilateral renal ischemia was induced in rats by clamping the left renal artery for 20, 60, and 120 min, respectively. One hour after the arterial clamp was removed, renal handling of gentamicin and paraaminohippurate (PAH) was studied over the next 2 hours; the kidneys were removed at the end of the experiments for determination of gentamicin and PAH content. The ischemic damage was evidenced by morphologic and functional changes. The glomerular filtration was decreased in proportion to the severity of ischemic injury. The excretion of gentamicin was highly correlated with GFR in normal and postischemic kidneys. In the cortex, ischemic injury resulted in reduced concentrations of gentamicin but markedly augmented those of PAH. The finding is consistent with the hypothesis that gentamicin is reabsorbed by the epithelial cells through the luminal membrane, whereas PAH enters via the peritubular membrane. In contrast, medullary concentrations of both compounds were similar, with suppression of uptake seen only after 120 min of ischemia. Conclusion. Ischemic damage impairs urinary elimination of gentamicin and the ability of renal parenchyma to retain the drug. Difference in uptake between gentamicin and PAH were unmasked in the postischemic kidneys.
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D005839:Gentamicins / Q000378:metabolism* / Q000652:urine; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051381:Rats; D010130:p-Aminohippuric Acid / Q000378:metabolism* / Q000652:urine
D000618:Aminohippuric Acids; D005839:Gentamicins; D010130:p-Aminohippuric Acid