Endotoxemic acute renal failure in awake rats

Am J Physiol. 1986 Jun;250(6 Pt 2):F1098-106. doi: 10.1152/ajprenal.1986.250.6.F1098.


The sequence of changes in renal function in endotoxemic acute renal failure (ARF) and the role of hypotension and systemic hemodynamics were evaluated in awake female Sprague-Dawley rats given an intravenous bolus of Escherichia coli endotoxin (20-40 mg/kg). After endotoxin ARF was abrupt in onset as glomerular filtration rate (GFR) fell promptly and progressively by 53% within 3.5 h, whereas renal blood flow decreased by 42% and renal vascular resistance nearly doubled. Systemic hemodynamics remained stable, including mean arterial blood pressure, cardiac output, and total peripheral resistance. Early endotoxemic ARF was associated with oliguria and sodium retention, a finding consistent with intact tubular function. Three and one-half hours after endotoxin, however, fractional water and sodium excretion were significantly increased. Ultrastructural studies then demonstrated sequestration of phagocytic leukocytes and intracellular edema in the peritubular capillaries with normal glomeruli. The decrease in GFR was spontaneously reversible within 7-9 days. Extracellular fluid volume expansion with saline either before or 24 h after administration of endotoxin failed to prevent the decrease in GFR or to normalize renal function. The data suggest that endotoxin has direct renal effects. The endothelial cells may be the primary target of endotoxin in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control
  • Animals
  • Endotoxins / pharmacology*
  • Escherichia coli*
  • Extracellular Space / metabolism
  • Female
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Kidney / pathology
  • Rats
  • Rats, Inbred Strains
  • Renal Circulation / drug effects
  • Sodium Chloride / therapeutic use
  • Time Factors
  • Wakefulness
  • p-Aminohippuric Acid / metabolism


  • Endotoxins
  • Sodium Chloride
  • p-Aminohippuric Acid