The Role of Nitric Oxide in Endotoxin-Elicited Hypodynamic Circulatory Failure

  • Daniel J. Brackett
  • Megan R. Lerner
  • Michael F. Wilson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 366)


Endothelial derived relaxation factor has recently been identified as the free radical nitric oxide.1 Nitric oxide is produced by endothelial cells, hepatocytes, Kupffer cells, neutrophils, and macrophages. All of these cells utilize L-arginine as a substrate for nitric oxide production2 and each has been documented as having a role in the development of septic and/or endotoxic shock. Recent evidence has suggested that nitric oxide may be a significant mediator in the acute hypotension, cardiovascular dysfunction, and tissue injury associated with septic shock; therefore, inhibition of nitric oxide has been proposed as a potential therapeutic treatment in septic patients.3 Our goal was to determine if the inhibition of nitric oxide synthesis attenuates the cardiovascular, metabolic, and pathological responses induced by endotoxin in the conscious rat. To accomplish this, NG-monomethyl-1-arginine (L-NMMA), an inhibitor of both Ca2+-dependent and Ca2+-independent nitric oxide synthesis, was utilized.


Nitric Oxide Systemic Vascular Resistance Nitric Oxide Synthesis Endotoxic Shock Endothelial Derive Relaxation Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    R.M.J. Palmer, A.G. Ferrige, and S. Moncada, Nitric oxide release accounts for the biologic activity of endothelium-derived relaxing factor, Nature 327: 524 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    S. Moncada, R.M.J. Palmer, and E.A. Higgs, Biosynthesis of nitric oxide from L-arginine: A pathway for the regulation of cell function and communication, Biochem. Pharmacol. 38: 1709 (1989).PubMedCrossRefGoogle Scholar
  3. 3.
    A. Pitros, D. Bennett, and P. Vallance, Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock, Lancet 338: 1557 (1991).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Daniel J. Brackett
    • 1
  • Megan R. Lerner
    • 1
  • Michael F. Wilson
    • 2
  1. 1.Departments of Surgery and AnesthesiologyUniversity of Oklahoma Health Sciences Center and the Veterans Affairs Medical CenterOklahoma CityUSA
  2. 2.Department of MedicineState University of New York Millard Fillmore HospitalsBuffaloUSA

Personalised recommendations