Pathophysiology of altered glomerular function in aminoglycoside-treated rats.
To evaluate the relative influences of gentamicin and tobramycin on glomerular function, we studied three groups of normal hydropenic rats. Group 1 had 8 rats that served as control. Group 2 had 9 rats that were given gentamicin (40 mg/kg of body wt per day for 10 days). Group 3 had 10 rats that received tobramycin instead of gentamicin. In addition, we attempted to suppress angiotensin II (AII) generation in two additional groups of rats and then study the glomerular response to gentamicin: in 6 rats, isotonic sodium chloride was substituted for tap water for drinking throughout the period of study (group 4), and in 7 other gentamicin-treated rats, captopril was given orally (group 5). A sixth group received captopril alone (group 6). Following gentamicin treatment in group 2, values for single nephron GFR (SNGFR) were markedly lower (21.7 +/- 2.1 nl/min) than they were in groups 1(35.7 +/- 1.4) or 3(34.1 +/- 2.9). Declines in whole kidney GFR in group 2 paralleled the fall in SNGFR. Reduction in SNGFR with gentamicin was due both to a marked decline in the glomerular capillary ultrafiltration coefficient, Kf, and in the initial glomerular plasma flow rate, QA. With saline administration (group 4), the decline in SNGFR was partially blunted, whereas with captopril (group 5) the effects of gentamicin on SNGFR, QA, and Kf were largely abolished. Morphologic studies revealed no discernible glomerular defects in any groups, whereas proximal tubule damage was evident with both aminoglycosides, irrespective of the state of the renin-angiotensin system. Thus, in the dosage used, gentamicin elicits greater impairment in glomerular function than does tobramycin, and by mechanism(s) that are at least partially responsive to suppression of AII generation.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000503:physiopathology; D009399:Nephrons / Q000503:physiopathology; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D014031:Tobramycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D012965:Sodium Chloride; D002216:Captopril; D014031:Tobramycin