FREE-RADICAL SCAVENGING BY LAZAROIDS IMPROVES RENAL BLOOD-FLOW DURINGSEPSIS

Background. Acute kidney failure in surgical patients is often related . to severe infection. Renal vasoconstriction is a major factor in the genesis of kidney failure. Reactive oxygen species (ROS) are known to mediate kidney injury after ischemia-reperfusion and are increased du ring sepsis. The role of ROS as mediators of intrarenal vasoconstricti on and renal dysfunction during sepsis is unclear. Lazaroids such as U 74389G are radical quenching antioxidants that inhibit ROS-induced lip id peroxidation. We sought to determine whether radical scavenging aff ected the renal microvascular response to a septic challenge. Methods. In vivo videomicroscopy was used to study the rat hydronephrotic kidn ey. Interlobular artery (ILA) diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured. U74389G or ve hicle was infused before a bolus injection of live Escherichia coli or normal saline solution.Results. U74389G alone had no effect on the re nal vessels or hemodynamics. E. coli caused preglomerular vasoconstric tion (ILA, -32%; afferent, -30% of baseline) and hypoperfusion (-66%) despite increased cardiac output (+54%). U74389G significantly attenua ted both the constriction (ILA, -16%; afferent, -9%) and hypoperfusion (-38%) but not increased cardiac output (+41%). Conclusions. E. coli bacteremia led to preglomerular vasoconstriction and hypoperfusion. In hibition of lipid peroxidation with the radical scavenger U74389G redu ced this effect without altering central hemodynamic responses. Free r adicals have a deleterious effect on the renal microcirculation during bacteremia, and these data suggest that antioxidants may be of value in preventing sepsis-associated kidney failure.