L-arginine augments nitric oxide production and mesenteric blood flow in ovine endotoxemia.
We studied the effects of administrating the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or the nitric oxide precursor, L-arginine, on hemodynamic variables and serum nitrate concentrations in an anesthetized ovine model of endotoxemia to assess the effects on regional visceral blood flow and to determine whether L-arginine availability limits nitric oxide production. Animals received Escherichia coli endotoxin (2 micrograms/kg) followed 2 h later by L-NAME (25 mg/kg), L-arginine (0.575 g/kg), or saline administered over 1 h followed by an infusion of the same dose over 8 h (n = 6 per group). Renal and mesenteric blood flow were measured by placement of electromagnetic flow probes, and serum nitrate concentrations were determined using vanadium III chloride or nitrate reductase reduction to nitric oxide or nitrite, respectively. The results showed L-NAME significantly increased systemic vascular resistance (P < 0.01), decreased serum nitrate concentrations (P < 0.05), and caused a transient reduction in mesenteric blood flow (P < 0.05). L-Arginine caused a reduction in systemic vascular resistance (P < 0.01), increased mesenteric blood flow (P < 0.001) and conductance (P < 0.05). There were no significant changes in renal arterial blood flow in either group. We conclude that the availability of L-arginine limits nitric oxide production in endotoxemia and, furthermore, that L-arginine administration in this model causes significant mesenteric vasodilatation. L-NAME administration had only limited effect on visceral blood flow despite a marked increase in systemic vascular resistance and a reduction in nitric oxide production.
Nuffield Department of Anaesthetics, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
K G
KG
Allman
A P
AP
Stoddart
M M
MM
Kennedy
J D
JD
Young
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001769:Blood / Q000378:metabolism; D002319:Cardiovascular System / Q000503:physiopathology; D004231:Diuresis; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D012756:Sheep; D013152:Splanchnic Circulation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D009566:Nitrates; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester