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 micrograms/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 less than 0.01, and 38% (LPS 0127:B8), P less than 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P less than 0.01) and total effective renal vascular resistance rose 70% (P less than 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 less than 0.03, and 33% (LPS 0127:B8), P less than 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P less than 0.03, and 24% (LPS 0127:B8), P less than 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (RA) which accounted for a reduction in the glomerular capillary hydraulic pressure (PGC). 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. Kf, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Thromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure in Endotoxemic Mice

“…Despite the accompanying hypotension, we found a marked renal vasoconstriction during endotoxemic shock, a finding implicating active involvement of vasoactive factors. Our results showing renal vasoconstriction and increased RVR agree with previous in vitro and in vivo studies in rodents (5,6,10).…”

“…However, both in experimental models of sepsis and in patients, changes in renal blood flow (RBF) vary widely. Micropuncture studies of renal hemodynamics during endotoxin infusion have shown that GFR and glomerular plasma flow are reduced, primarily as a result of increased afferent arteriolar resistance (5). Other studies show that intraluminal application of LPS in a bloodperfused juxtamedullary nephron preparation elicits a sustained vasoconstriction of the arcuate artery, interlobular artery, and afferent arteriole, without affecting efferent arteriolar diameter.…”

Prevention and Treatment of Acute Renal Failure in Sepsis

“…Cyclooxygenase inhibition with indomethacin had a markedly protective effect on glomerular hemodynamics in endotoxemic rats (77). A selective thromboxane synthetase inhibitor attenuated the renal effects of LPS in the rat (78) and protected the kidney in sheep with hyperdynamic septic shock (79).…”

Renal Hemodynamics in AKI

“…[2][3][4][5] The causative contribution of renal blood flow (RBF) to kidney dysfunction is particularly puzzling in sepsis, and there is widespread disagreement as to whether RBF is reduced, normal, or even increased. 2,3,[6][7][8] In the few large animal and clinical studies, the patterns of RBF in AKI and its relation with systemic hemodynamics are highly variable. 3,6 Absence of benefit of vasodilator therapy in human sepsis-associated AKI 9 may be explained by variability in blood flow.…”