Renal microvascular responses to sepsis are dependent on nitric oxide.

Nitric oxide (NO) is an important mediator of the hemodynamic response to sepsis; however, its visceral microcirculatory effects are largely unknown. To determine the role of NO in renal microvascular responses to bacteremia, rat hydronephrotic kidneys with intact neurovascular supplies were exteriorized into a tissue bath. Videomicroscopy was used to measure vessel diameters (interlobular artery, ILA; afferent arteriole, AFF; efferent arteriole, EFF) and optical Doppler velocimetry was used to quantitate ILA flow. In controls, topical L-arginine (L-Arg; 10(-4) M), the NO synthase (NO-S) substrate, resulted in mild pre- and postglomerular dilation and increased flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME: 10(-4) M) caused preglomerular constriction (ILA = -22%; AFF = -20% from baseline) and reduced ILA flow by 39%, while postglomerular diameters (EFF) were unchanged. Bacteremic rats had similar alterations (ILA = -22%; AFF = -20%; flow = -56%). Topical L-NAME in bacteremic rats resulted in further constriction (ILA = -38%; AFF = -37%), decreased ILA flow (-75%) and constricted EFF (-30%). L-Arg ameliorated constriction (ILA = -11%; AFF = -7%) and flow (-34%) during bacteremia. We conclude that: (1) NO is important in basal preglomerular tone; (2) Escherichia coli causes selective preglomerular constriction and hypoperfusion; (3) maintenance of EFF tone during bacteremia is NO dependent; and (4) different pre- and postglomerular NO mechanisms exist during basal and bacteremic states. These data indicate that NO is an important mediator of renal microvascular responses to sepsis.