Renal effects of endotoxin in the male rat
Churchill, P.C.; Bidani, A.K.; Schwartz, M.M.
American Journal of Physiology 253(2 Pt 2): F244-F250
1987
ISSN/ISBN: 0002-9513 PMID: 3303973 Document Number: 297915
A new nodel of acute reduction in renal function induced by a 2-h infusion of endotoxin (Escherichia coli 026:B6 lipopolysaccharide, 5 mg .cntdot. kg-1 .cntdot. 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 .cntdot. kg-1 .cntdot. min-1 (P < 0.0005), and p-aminophippuric acid clearance was reduced from 23.7 .+-. 0.8 to 15.0 .+-. 1.8 ml .cntdot. kg-1 .cntdot. min-1 (P < 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 0.56 .+-. 0.09%, P < 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.