Is endotoxin-induced hypotension related to nitric oxide formation?
Nitric oxide (NO), an endothelium-derived relaxing factor (EDRF), is released by different types of cells under the influence of endotoxin and various cytokines: a causative role of endothelium-derived NO in the endotoxin-induced hypotension has thus been suggested. To test the hypothesis that NO may be involved in the acute hypotension following endotoxin challenge, we administered a competitive inhibitor of NO synthase, L-N-monomethylarginine (L-NMMA) to anesthetized dogs in the presence and absence of endotoxin. Dogs were randomly allocated to three groups. Group 1 (n = 3) was given Escherichia coli endotoxin (3 mg/kg, i.v.), group 2 (n = 3) was given L-NMMA (5 mg/kg, i.v. bolus) 15 min after endotoxin and group 3 (n = 3) was given L-NMMA only. One additional dog was given L-arginine (100 mg/kg, i.v. bolus) after L-NMMA and endotoxin to reverse the inhibition of NO synthase. In each animal, saline was infused intravenously throughout the experiment to restore and maintain pulmonary artery occluded pressure at baseline level. After L-NMMA, the increases in mean arterial pressure were similar in group 2 (from 55 +/- 18 to 75 +/- 15 mm Hg, p < 0.01) and in group 3 (from 107 +/- 27 to 128 +/- 24 mm Hg, p < 0.01). Systemic vascular resistance increased from 2,994 +/- 72 to 3,658 +/- 673 dyn.s.cm-5 (p < 0.01) in group 3. Group 1 had lower plasma lactate levels than group 2 (3.5 +/- 2.3 +/- vs. 2.0 +/- 1.6 mEq/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Preiser
J C
JC
Department of Intensive Care, Erasme University Hospital, Free University of Brussels.
Zhang
H
H
Wachel
D
D
Boeynaems
J M
JM
Buurman
W
W
Vincent
J L
JL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D011897:Random Allocation; D012772:Shock, Septic / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019323:omega-N-Methylarginine
D004731:Endotoxins; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen