Reduction of renal blood flow and proximal bicarbonate reabsorption in rats by gentamicin.
Although aminoglycoside-induced acute renal failure occurs commonly, little is known about the mechanisms which alter renal hemodynamics. In sodium-depleted Sprague-Dawley rats treated with gentamicin, we measured RBF and GFR at the onset of this model of nephrotoxic acute renal failure. After 10 days of sodium chloride depletion, one group of rats received a single injection of gentamicin, 100 mg/kg, while control animals received the gentamicin vehicle. Twenty-four hours later, PCr and UNa/UCr were similar in both groups. CIn was unchanged, but RBF was reduced significantly (12.40 +/- 1.33 vs. 16.89 +/- 1.24 ml/min). Micropuncture studies revealed that although SNGFR was unchanged, end-proximal and early distal flow rates were increased significantly. End-proximal TFCl was reduced significantly in gentamicin-treated animals when compared to controls (130.7 +/- 3.9 vs. 149.5 +/- 4.1 mEq/liter). Early distal TFCl was also reduced significantly (32.4 +/- 2.0 vs. 44.3 +/- 1.4 mEq/liter). In other rats, 24 hr after a second injection of gentamicin, PCr and UNa/UCr were increased significantly and both GFR and RBF were reduced significantly. We conclude that the earliest hemodynamic change in gentamicin-induced acute renal failure is a reduction in RBF which precedes any change in GFR. A single dose of gentamicin also impairs proximal bicarbonate and water reabsorption and reduces end-proximal and early distal chloride concentration.
D000042:Absorption; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*
D001639:Bicarbonates; D005839:Gentamicins; D003404:Creatinine