Nitric Oxide, Oxidative Stress, Immune Response and Critical Care

Claudio Napoli, Ettore Crimi, Sharon Williams-Ignarro, Filomena de Nigris, Louis J. Ignarro

Research output: Contribution to journalArticlepeer-review


Nitric oxide (NO), a gaseous free radical produced by a wide variety of cell types, has emerged as a significant signaling molecule involved in many physiological systems. Synthesized by a family of enzymes known as NO synthases (NOS), NO exerts its effects primarily by cyclic guanosine-monophosphate (cGMP)-dependent mechanisms, involving activation of soluble guanylate cyclase (sGC). Critical illness is associated with oxidative stress that could exacerbate organ injury and thus overall outcome. The small amounts of nitric oxide (NO) produced physiologically have beneficial effects contributing to the maintenance of normal homeostasis. Increased and persistent production of NO, as observed in critical illnesses, can lead to an overwhelming inflammatory response and tissue injury, promoting cell injury and death. Microcirculatory dysfunction, as a result of an imbalance between NO availability and reactive oxygen species, plays an important role in the pathogenesis of critical illnesses. The most important physiologic factor for NO synthesis is shear stress; that is, a tangential distortion of the endothelial cells produced by blood flow. NO is also released in response to pharmacological agonists such as acetylcholine. NO has been recognized as an important mediator in liver I/R, occurring during transplantation, surgery, hemorrhagic shock, and late sepsis. While eNOS can exert a protective effect on the liver, the excessive NO production from iNOS with associated peroxynitrite formation is generally considered to mediate hepatic injury. The enhanced production of NO contributes to myocardial dysfunction, mediating the depressant effects of proinflammatory cytokines. NO can reduce myocardial contractility by reducing the calcium affinity of contractile apparatus and cause direct myocyte damage by peroxynitrite production.

Original languageEnglish
Pages (from-to)755-772
Number of pages18
JournalUnknown Journal
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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