Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity

José R. Romero, Sandra M. Suzuka, Ronald L. Nagel, Mary E. Fabry

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Nitric oxide (NO), essential for maintaining vascular tone, is produced from arginine by nitric oxide synthase. Plasma arginine levels are low in sickle cell anemia, and it is reported here that low plasma arginine is also found in our sickle transgenic mouse model that expresses human α, human βs, and human βS-Antilles and is homozygous for the mouse βmajor deletion (S+S-Antilles). S+S-Antilles mice were supplemented with a 4-fold increase in arginine that was maintained for several months. Mean corpuscular hemoglobin concentration (MCHC) decreased and the percent high-density red cells was reduced. Deoxy K+ efflux is characteristic of red cells in sickle cell disease and contributes to the disease process by increasing the MCHC and rendering the cells more susceptible to polymer formation. This flux versus the room air flux was reduced in S+S-Antilles red cells from an average value of 1.6 ± 0.3 mmol per liter of red cells × minute (FU) in nonsupplemented mice to 0.9 ± 0.3 FU (n = 4, P < .02, paired test) in supplemented mice. In room air, Vmax of the Ca++-activated K+ channel (Gardos) was reduced from 4.1 ± 0.6 FU (off diet) to 2.6 ± 0.4 FU (n = 7 and 8, P < .04, t test) in arginine-supplemented mice versus clotrimazole. In conclusion, the major mechanism by which arginine supplementation reduces red cell density (MCHC) in S+S-Antilles mice is by inhibiting the Ca++-activated K+ channel.

Original languageEnglish (US)
Pages (from-to)1103-1108
Number of pages6
JournalBlood
Volume99
Issue number4
DOIs
StatePublished - Feb 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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