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


RESULTS
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.


CONCLUSIONS
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.
Weinberg
J Brice
JB
Duke University and VA Medical Centers, Durham, North Carolina 27705, USA. brice@duke.edu
Lopansri
Bert K
BK
Mwaikambo
Esther
E
Granger
Donald L
DL
D000740:Anemia / Q000097:blood / Q000469:parasitology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001682:Biological Availability; D002248:Carbon Monoxide / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008288:Malaria / Q000097:blood / Q000473:pathology*; D016778:Malaria, Falciparum / Q000097:blood / Q000473:pathology*; D009569:Nitric Oxide / Q000097:blood* / Q000502:physiology
D009569:Nitric Oxide; D002248:Carbon Monoxide; D001120:Arginine