Skip to main content

Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria.

Publication ,  Journal Article
Yeo, TW; Lampah, DA; Gitawati, R; Tjitra, E; Kenangalem, E; McNeil, YR; Darcy, CJ; Granger, DL; Weinberg, JB; Lopansri, BK; Price, RN ...
Published in: J Exp Med
October 29, 2007

Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in SM but can be improved by l-arginine in cardiovascular disease. In an observational study in Indonesia, we measured endothelial function using reactive hyperemia-peripheral arterial tonometry (RH-PAT) in 51 adults with SM, 48 patients with moderately severe falciparum malaria (MSM), and 48 controls. The mean RH-PAT index was lower in SM (1.41; 95% confidence interval [CI] = 1.33-1.47) than in MSM (1.82; 95% CI = 1.7-2.02) and controls (1.93; 95% CI = 1.8-2.06; P < 0.0001). Endothelial dysfunction was associated with elevated blood lactate and measures of hemolysis. Exhaled NO was also lower in SM relative to MSM and controls. In an ascending dose study of intravenous l-arginine in 30 more patients with MSM, l-arginine increased the RH-PAT index by 19% (95% CI = 6-34; P = 0.006) and exhaled NO by 55% (95% CI = 32-73; P < 0.0001) without important side effects. Hypoargininemia and hemolysis likely reduce NO bioavailability. Endothelial dysfunction in malaria is nearly universal in severe disease, is reversible with l-arginine, and likely contributes to its pathogenesis. Clinical trials in SM of adjunctive agents to improve endothelial NO bioavailability, including l-arginine, are warranted.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

October 29, 2007

Volume

204

Issue

11

Start / End Page

2693 / 2704

Location

United States

Related Subject Headings

  • Reference Values
  • Plasmodium falciparum
  • Ornithine
  • Nitric Oxide
  • Middle Aged
  • Male
  • Malaria, Falciparum
  • Leukocyte Count
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yeo, T. W., Lampah, D. A., Gitawati, R., Tjitra, E., Kenangalem, E., McNeil, Y. R., … Anstey, N. M. (2007). Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med, 204(11), 2693–2704. https://doi.org/10.1084/jem.20070819
Yeo, Tsin W., Daniel A. Lampah, Retno Gitawati, Emiliana Tjitra, Enny Kenangalem, Yvette R. McNeil, Christabelle J. Darcy, et al. “Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria.J Exp Med 204, no. 11 (October 29, 2007): 2693–2704. https://doi.org/10.1084/jem.20070819.
Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil YR, et al. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med. 2007 Oct 29;204(11):2693–704.
Yeo, Tsin W., et al. “Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria.J Exp Med, vol. 204, no. 11, Oct. 2007, pp. 2693–704. Pubmed, doi:10.1084/jem.20070819.
Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil YR, Darcy CJ, Granger DL, Weinberg JB, Lopansri BK, Price RN, Duffull SB, Celermajer DS, Anstey NM. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med. 2007 Oct 29;204(11):2693–2704.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

October 29, 2007

Volume

204

Issue

11

Start / End Page

2693 / 2704

Location

United States

Related Subject Headings

  • Reference Values
  • Plasmodium falciparum
  • Ornithine
  • Nitric Oxide
  • Middle Aged
  • Male
  • Malaria, Falciparum
  • Leukocyte Count
  • Immunology
  • Humans