Nitric Oxide in Sepsis and Nitric Oxide in Sepsis and ARDS

  • H. Zhang
  • T. E. Stewart
  • J.-L. Vincent
Conference paper


Septic shock, a major clinical problem with mortality rates of up to 70%, is characterized by systemic hypotension, impaired tissue O2 extraction capabilities and myocardial depression. Much interest has been focused on the role of nitric oxide (NO) in septic shock during the last decade. Following the discovery of the NO radical it was clear that NO could play a role in the vascular relaxation and hypotension during sepsis and endotoxaemia. In vitro studies showed that isolated macrophages produced increased amounts of nitrate and nitrite upon stimulation with lipopolysaccharides [1, 2]. This increase was shown to be caused by the increased production of NO, which was dependent on the presence of L-arginine and could be inhibited by analogs of L-arginine. The NO synthase enzyme responsible for production of NO in macrophages is inducible (iNOS) and differs from the constitutive NO synthase (cNOS) in endothelial cells. The cNOS is calcium and calmodulin dependent and releases small amounts of NO, whereas the iNOS is calcium and calmodulin independent and releases large amounts of NO for a prolonged period of time. The iNOS enzyme shown in macrophages can also be found in neutrophils, hepatocytes, myocardial cells and vascular smooth muscle cells stimulated with endotoxin or cytokines [3, 4, 5]. iNOS is expressed under the influence of endotoxin and several cytokines like tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-Iβ) and interferon-γ [4, 6]. In general, one can say that cNOS plays a physiological role in maintaining organ perfusion, whereas iNOS plays a more pathological role (as in sepsis and endotoxaemia) leading to the production of excessive amounts of NO resulting in vascular relaxation and tissue damage [7].


Nitric Oxide Nitric Oxide Septic Shock Methylene Blue Nitric Oxide Synthesis 
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Copyright information

© Springer-Verlag Italia 1999

Authors and Affiliations

  • H. Zhang
    • 1
  • T. E. Stewart
    • 1
  • J.-L. Vincent
    • 2
  1. 1.Division of Respiratory Medicine, Mount Sinai HospitalToronto UniversityTorontoCanada
  2. 2.Dept. of Intensive Care, Erasme University HospitalFree University of BrusselsBrusselsBelgium

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