The
acute renal failure associated with
septic shock is associated with a high mortality despite dialytic
therapies.
Endotoxemia leads to marked changes in the distribution of intrarenal perfusion that may be independent of alterations in total renal blood flow or systemic hemodynamics. Modulation of this intrarenal redistribution may protect against
acute renal failure. This study examines the effect of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (
carboxy-PTIO), a scavenger of
nitric oxide (NO), on systemic and intrarenal hemodynamics measured by
laser Doppler flowmetry following the induction of
endotoxemia in the anesthetized rat. Infusion of
lipopolysaccharide (LPS) led to a prompt reduction in
inulin clearance at 60 min, which remained reduced for 6 h in saline-treated rats. Administration of
carboxy-PTIO led to a sustained increase in
inulin clearance over 360 min post-LPS. During
endotoxemia, cortical perfusion fell acutely by 29 +/- 8%, whereas medullary perfusion increased by 71 +/- 11%. The increase in medullary perfusion was potently and selectively inhibited by
carboxy-PTIO. We propose that inhibition of medullary
hyperemia maintains glomerular hydrostatic pressure, thus leading to the improved renal function during
endotoxemia and that scavenging of NO may prove to be a useful therapeutic option in the
acute renal failure associated with
septic shock.