AJP - Renal Physiology, Vol 253, Issue 2 244-F250, Copyright © 1987 by American Physiological Society
Renal effects of endotoxin in the male rat
P. C. Churchill, A. K. Bidani and M. M. Schwartz
A new model of acute reduction in renal function induced by a 2-h infusion
of endotoxin (Escherichia coli 026:B6 lipopolysaccharide, 5 mg X kg-1 X
h-1) was developed in the anesthetized male rat. In the absence of
significant glomerular fibrin deposition, inulin clearance (glomerular
filtration rate, GFR) was reduced from 8.50 +/- 0.34 to 4.01 +/- 0.45 ml X
kg-1 X min-1 (P less than 0.0005), and p-aminohippuric acid clearance was
reduced from 23.7 +/- 0.8 to 15.0 +/- 1.8 ml X kg-1 X min-1 (P less than
0.0005), indicating a hemodynamic basis for the reduction in GFR. The lack
of morphological tubular injury and a decreased fractional Na excretion
(from 2.63 +/- 0.27 to 0.54 +/- 0.09%, P less than 0.00005) exclude a
significant contribution of tubular mechanisms to the reduction in GFR.
Administration of theophylline, a competitive adenosine receptor
antagonist, concurrently with or immediately after the endotoxin infusion,
restored inulin and PAH clearances and fractional Na excretion toward
normal. Moreover, the renal effects of endotoxin were mimicked by
intravenous administration of N6-(L-phenylisopropyl)-adenosine (L-PIA), an
adenosine receptor agonist, and the effects of L-PIA in turn were also
antagonized by theophylline. These data suggest that adenosine plays a
significant role in mediating the hemodynamic derangements of this model.
