Nitric Oxide and Cardiovascular Dysfunction in Sepsis

Author(s): Jamil Assreuy.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets

Volume 6 , Issue 2 , 2006

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Abstract:

Sepsis and septic shock are the major causes of morbidity and mortality in critically ill patients. During the onset of sepsis, a massive inflammatory reaction involving chemical mediators such as cytokines and chemokines and inflammatory cells such as the polymorphonuclear neutrophil and macrophage takes place. In addition to this systemic inflammatory process, sepsis and septic shocks cause a profound decrease in the peripheral vasomotor tone leading to a great decrease in the peripheral resistance. This event is central to derangement of hemodynamic and perfusional parameters. Nitric oxide (NO) is produced by several cell types and has been implicated in a wide range of physiological and pathological processes, with both detrimental and beneficial effects. There is a wealth of data implicating NO as a key player in all cardiac, vascular, renal and pulmonary derangements of sepsis and septic shock. Clinical assays trying to improve sepsis by inhibiting NO formation by NO synthases have met with failure, probably due to the lack of selectivity of inhibitors towards NOS isoforms. Notwithstanding the search for selective inhibitors, a better understanding of the NO molecular effector mechanisms may provide new opportunities for therapy development. Some of these NO effector mechanisms are discussed, including guanylate cyclase, nitrosothiols, potassium channels, reactive oxygen species and gene expression in the context of sepsis. Thus, more research on the relationship between NO and sepsis is clearly needed and warranted and may provide new therapeutic targets to treat sepsis and septic shock.

Keywords: Sepsis, septic shock, nitric oxide, hypotension, vascular hyporesponsiveness, guanylate cyclase, potassium channel, nitrosothiol

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2006
Page: [165 - 173]
Pages: 9
DOI: 10.2174/187153006777442314
Price: $58

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