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 109Escherichia coliintravenously. 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; 10minus;4M) did not affect diameters or flow. Inhibition of NO-S byNomega;minus;nitro-L-arginine methyl ester (L-NAME; 10minus;4M) caused constriction (A1 = minus;18percnt;; A3 = minus;24percnt; from baseline diameter) and reduced A1 flow by 62percnt;. These alterations were similar to bacteremic controls (A1 = minus;20percnt;; A3 = minus;18percnt;; A1 flow = minus;42percnt;), despite the increased cardiac output (plus;21percnt;). L-NAME treatment of bacteremic rats resulted in further constriction (A1 = minus;31percnt;; A3 = minus;32percnt;) and decreased A1 flow (minus;75percnt;). Topical L-ARG (10minus;4M) ameliorated constriction (A1 = minus;6percnt;; A3 = plus;7percnt;) and improved blood flow (minus;5percnt;) 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.
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