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Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity.
Blood 2002; 99(4):1103-8Blood

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 alpha, human beta(S), and human beta(S-Antilles) and is homozygous for the mouse beta(major) 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 x minute (FU) in nonsupplemented mice to 0.9 +/- 0.3 FU (n = 4, P < .02, paired t test) in supplemented mice. In room air, V(max) 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.

Authors+Show Affiliations

Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11830454

Citation

Romero, José R., et al. "Arginine Supplementation of Sickle Transgenic Mice Reduces Red Cell Density and Gardos Channel Activity." Blood, vol. 99, no. 4, 2002, pp. 1103-8.
Romero JR, Suzuka SM, Nagel RL, et al. Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood. 2002;99(4):1103-8.
Romero, J. R., Suzuka, S. M., Nagel, R. L., & Fabry, M. E. (2002). Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood, 99(4), pp. 1103-8.
Romero JR, et al. Arginine Supplementation of Sickle Transgenic Mice Reduces Red Cell Density and Gardos Channel Activity. Blood. 2002 Feb 15;99(4):1103-8. PubMed PMID: 11830454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. AU - Romero,José R, AU - Suzuka,Sandra M, AU - Nagel,Ronald L, AU - Fabry,Mary E, PY - 2002/2/7/pubmed PY - 2002/4/26/medline PY - 2002/2/7/entrez SP - 1103 EP - 8 JF - Blood JO - Blood VL - 99 IS - 4 N2 - 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 alpha, human beta(S), and human beta(S-Antilles) and is homozygous for the mouse beta(major) 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 x minute (FU) in nonsupplemented mice to 0.9 +/- 0.3 FU (n = 4, P < .02, paired t test) in supplemented mice. In room air, V(max) 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/11830454/Arginine_supplementation_of_sickle_transgenic_mice_reduces_red_cell_density_and_Gardos_channel_activity_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&amp;pmid=11830454 DB - PRIME DP - Unbound Medicine ER -