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.
Spain
D A
DA
Department of Surgery, University of Louisville, Kentucky.
Wilson
M A
MA
Bloom
I T
IT
Garrison
R N
RN
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016470:Bacteremia / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester