Renal function and glomerular hemodynamics in male endotoxemic rats

Abstract

The renal effects of a single intravenous dose of two different E. coli lipopolysaccharides (LPS 0111:B4 and LPS 0127:B8), at the same dose of 100 μg/kg, were evaluated in euvolemic Munich-Wistar (MW) rats by whole kidney clearance techniques and micropuncture studies. Following LPS infusion, a significant decrease (8%) in mean BP was observed only in the LPS 0127:B8 treated group. Inulin clearance fell 57% (LPS 0111:B4), P < 0.01, and 38% (LPS 0127:B8), P < 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P < 0.01) and total effective renal vascular resistance rose 70% (P < 0.03) in response to LPS 0111:B4. No significant change in PAH clearance was noted in the LPS 0127:B8 group. Superficial single nephron glomerular filtration rate (SNGFR) was reduced 69% (LPS 0111:B4), P < 0.03, and 33% (LPS 0127:B8), P < 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P < 0.03, and 24% (LPS 0127:B8), P < 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (R(A)) which accounted for a reduction in the glomerular capillary hydraulic pressure (P(GC)). There was no change in the proximal tubular pressure in either group and, therefore, the net transcapillary hydraulic pressures were reduced. No measurable change in the ultrafiltration coefficient, K(f), was observed in either group. In a second set of protocols, the effect of prior administration of indomethacin or captopril on LPS 0111:B4 action was investigated. A significant decrease in BP occurred when animals were pretreated with captopril. Both indomethacin and captopril prevented the renal effects of LPS 0111:B4. The data indicate that lipopolysaccharides affect the kidney primarily by causing a selective increase in R(A). They also indicate that the nephrotoxic potential of the lipopolysaccharides studied are not equipotent. Finally, the results from indomethacin and captopril groups suggest that hormonal alterations play a role in the LPS-induced renal hemodynamic changes.