The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described.
Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including
sepsis, and we hypothesized that alterations in
nitric oxide contribute to redistribution of renal blood flow during
sepsis. The current study used
laser Doppler fluximetry and clearance of
p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli
bacteremia, with and without inhibition of
nitric oxide. Inhibition of
nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux.
Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of
nitric oxide synthase during
bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that
nitric oxide regulates renovascular tone during normal conditions and
bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during
sepsis.