NITRIC-OXIDE MEDIATES REDISTRIBUTION OF INTRARENAL BLOOD-FLOW DURING BACTEREMIA

The normal or hyperdynamic circulatory response during the early phase s of the systemic septic response is associated with renal microvascul ar constriction and can result in renal dysfunction, Intrarenal redist ribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or ele vated renal blood flow, but the mechanisms of this response are not we ll described, Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions inclu ding sepsis, and we hypothesized that alterations in nitric oxide cont ribute to redistribution of renal blood flow during sepsis, The curren t study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribu tion of blood flow during basal conditions and during normodynamic Esc herichia coli bacteremia, with and without inhibition of nitric oxide, Inhibition of nitric oxide in normal animals resulted in a decrease i n ERPF (-19%) with a decrease in cortical flux (-39%) without alterati on of medullary flux, Bacteremia resulted in a decrease in cortical fl ow (-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 nit ric oxide regulates renovascular tone during normal conditions and bac teremia, and indicate that it is a prime mediator of intrarenal redist ribution of blood flow during sepsis.