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 deter mine the role of NO in the small intestinal (SI) microcirculation, an intact SI loop was exteriorized from decerebrate rats into a controlle d Krebs' bath, Bacteremic rats received 10(9) Escherichia coli intrave nously. Videomicroscopy was used to measure arteriolar diameters (A1,A 3) and optical Doppler velocimetry to quantitate flow. In controls, to pical NO synthase (NO-S) substrate L-arginine (L-ARG; 10(-4) M) did no t affect diameters or flow. Inhibition of NO-S byN omega-nitro-L-argin ine methyl ester (L-NAME; 10(-4) Rn) caused constriction (A1 = -18%; A 3 = -24% from baseline diameter) and reduced A1 flow by 62%. These alt erations were similar to bacteremic controls (A1 = -20%; A3 = -18%; A1 flow = -42%), despite the increased cardiac output (+21%). L-NAME tre atment of bacteremic rats resulted in further constriction (A1 = -31%; A3 = -32%) and decreased A1 flow (-75%). Topical L-ARG (10(-4) M) ame liorated constriction (A1 = -6%; A3 = +7%) and improved blood flow (-5 %) during bacteremia. We conclude that: 1) NO is important for basal S I microvascular tone; 2) bacteremia causes SI arteriolar constriction and hypoperfusion; 3) NO-S inhibition during sepsis may exacerbate SI vasoconstriction and hypoperfusion.