AJP - Renal Physiology, Vol 250, Issue 6 1098-F1106, Copyright © 1986 by American Physiological Society
Endotoxemic acute renal failure in awake rats
D. Kikeri, J. P. Pennell, K. H. Hwang, A. I. Jacob, A. V. Richman and J. J. Bourgoignie
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.
