L-ARGININE AUGMENTS NITRIC-OXIDE PRODUCTION AND MESENTERIC BLOOD-FLOWIN OVINE ENDOTOXEMIA

We studied the effects of administrating the nitric oxide synthase inh ibitor, N-G-nitro-L-arginine methyl ester (L-NAME), or the nitric oxid e precursor, L-arginine, on hemodynamic variables and serum nitrate co ncentrations in an anesthetized ovine model of endotoxemia to assess t he effects on regional visceral blood flow and to determine whether L- arginine availability limits nitric oxide production. Animals received Escherichia coli endotoxin (2 mu g/kg) followed 2 h later by L-NAME ( 25 mg/kg), L-arginine (0.575 g/kg), or saline administered over 1 h fo llowed by an infusion of the same dose over 8 h (n = 6 per group). Ren al and mesenteric blood flow were measured by placement of electromagn etic flow probes, and serum nitrate concentrations were determined usi ng vanadium III chloride or nitrate reductase reduction to nitric oxid e or nitrite, respectively. The results showed L-NAME significantly in creased systemic vascular resistance (P < 0.01), decreased serum nitra te concentrations (P < 0.05), and caused a transient reduction in mese nteric blood flow (P < 0.05). L-Arginine caused a reduction in systemi c vascular resistance (P < 0.01), increased mesenteric blood flow (P < 0.001) and conductance (P < 0.0001), and increased serum nitrate conc entrations (P < 0.05). There were no significant changes in renal arte rial blood flow in either group. We conclude that the availability of L-arginine limits nitric oxide production in endotoxemia and, furtherm ore, that L-arginine administration in this model causes significant m esenteric vasodilatation. L-NAME administration had only limited effec t on visceral blood flow despite a marked increase in systemic vascula r resistance and a reduction in nitric oxide production.