Role of nitric oxide in the small intestinal microcirculation during bacteremia.
Nitric oxide (NO) is an important mediator of the hemodynamic effects of sepsis; however, its microcirculatory effects are unknown. To determine the role of NO in the small intestinal (SI) microcirculation, an intact SI loop was exteriorized from decerebrate rats into a controlled Krebs' bath. Bacteremic rats received 10(9) Escherichia coli intravenously. Videomicroscopy was used to measure arteriolar diameters (A1, A3) and optical Doppler velocimetry to quantitate flow. In controls, topical NO synthase (NO-S) substrate L-arginine (L-ARG; 10(-4) M) did not affect diameters or flow. Inhibition of NO-S by N omega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) caused constriction (A1 = -18%; A3 = -24% from baseline diameter) and reduced A1 flow by 62%. These alterations were similar to bacteremic controls (A1 = -20%; A3 = -18%; A1 flow = -42%), despite the increased cardiac output (+21%). L-NAME treatment of bacteremic rats resulted in further constriction (A1 = -31%; A3 = -32%) and decreased A1 flow (-75%). Topical L-ARG (10(-4) M) ameliorated constriction (A1 = -6%; A3 = +7%) and improved blood flow (-5%) during bacteremia. We conclude that: 1) NO is important for basal SI microvascular tone; 2) bacteremia causes SI arteriolar constriction and hypoperfusion; 3) NO-S inhibition during sepsis may exacerbate SI vasoconstriction and hypoperfusion.
Spain
D A
DA
Department of Surgery, University of Louisville, Kentucky 40292, USA.
Wilson
M A
MA
Bar-Natan
M F
MF
Garrison
R N
RN
D000594:Amino Acid Oxidoreductases / Q000032:analysis; D000818:Animals; D016470:Bacteremia / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases