Nitric Oxide as a Mediator of the Vascular Derangements of Sepsis and Endotoxemia

  • J. R. Parratt
  • J. C. Stoclet
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 16)


It is a concept, fundamental to physiology and pharmacology, that if a cellular recognition site exists for a chemical quite foreign to the body, then a similar recognition site, or receptor, might also be the means by which an endogenous ligand, similar to that foreign chemical, also results in cellular activation. Thus, the demonstration of specific recognition sites for morphine led to the search for, and discovery of, endogenous opioid-like peptides. More recently, there has been increasing evidence for the presence within the body of an “endogenous digitalis”. It is now well over a century since T. Lauder Brunton described the beneficial effects of amyl nitrite in patients with angina pectoris, and less than 30 years ago since the precise vascular and cellular mechanisms of action of organic nitrates and nitrites were elucidated. The finding that this depends on activation of soluble guanylyl cyclase within vascular smooth muscle cells, with a subsequent formation of an intracellular second messenger, cyclic 3–5-guanosine monophosphate (cGMP), was one of the factors that led eventually to the discovery of an “endogenous nitrodilator” nitric oxide (NO), the formation of which is responsible for the action of clinically useful nitrodilators such as glyceryl tri-nitrate, nitroprusside and sydnonimines such as molsidomine (and its active metabolite SIN-1) which act on the blood vessel walls by “donating” NO. Endogneous NO is now known to be produced from the amino-acid L-argini-ne in a variety of cells [1] including vascular endothelium [2, 3], macrophages [4], neutrophils [5, 6] and platelets [7, 8]. In endothelial cells, it is this endogenous nitrodilator, NO (or a closely related compound releasing this free radical) that is responsible of the effects of the endothelium-derived relaxing factor (EDRF) originally described by Furchgott and Zawadzki in 1980 [9], who discovered that the ability of acetycholine to relax vascular smooth muscle depended on the integrity of the endothelium and the release from it of a diffusible substance.


Nitric Oxide Nitric Oxide Methylene Blue Aortic Ring Circ Shock 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • J. R. Parratt
  • J. C. Stoclet

There are no affiliations available

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