Arginine, nitric oxide, carbon monoxide, and endothelial function in severe malaria.

Journal Article (Journal Article;Review)

PURPOSE OF REVIEW: Parasiticidal therapy of severe falciparum malaria improves outcome, but up to 30% of these patients die despite best therapy. Nitric oxide is protective against severe disease, and both nitric oxide and arginine (the substrate for nitric oxide synthase) are low in clinical malaria. Parasitized red blood cell interactions with endothelium are important in the pathophysiology of malaria. This review describes new information regarding nitric oxide, arginine, carbon monoxide, and endothelial function in malaria. RECENT FINDINGS: Low arginine, low nitric oxide production, and endothelial dysfunction are common in severe malaria. The degree of hypoargininemia and endothelial dysfunction (measured by reactive hyperemia-peripheral artery tonometry) is proportional to parasite burden and severity of illness. Plasma arginase (an enzyme that catabolizes arginine) is elevated in severe malaria. Administering arginine intravenously reverses hypoargininemia and endothelial dysfunction. The cause(s) of hypoargininemia in malaria is unknown. Carbon monoxide (which shares certain functional properties with nitric oxide) protects against cerebral malaria in mice. SUMMARY: Replenishment of arginine and restoration of nitric oxide production in clinical malaria should diminish parasitized red blood cells adherence to endothelium and reduce the sequelae of these interactions (e.g. cerebral malaria). Arginine therapy given in addition to conventional antimalaria treatment may prove to be beneficial in severe malaria.

Full Text

Duke Authors

Cited Authors

  • Weinberg, JB; Lopansri, BK; Mwaikambo, E; Granger, DL

Published Date

  • October 2008

Published In

Volume / Issue

  • 21 / 5

Start / End Page

  • 468 - 475

PubMed ID

  • 18725795

Pubmed Central ID

  • PMC2732119

Electronic International Standard Serial Number (EISSN)

  • 1473-6527

Digital Object Identifier (DOI)

  • 10.1097/QCO.0b013e32830ef5cf


  • eng

Conference Location

  • United States