PMID- 11830454
OWN - NLM
STAT- MEDLINE
DCOM- 20020425
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 4
DP  - 2002 Feb 15
TI  - Arginine supplementation of sickle transgenic mice reduces red cell density and 
      Gardos channel activity.
PG  - 1103-8
AB  - 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.
FAU - Romero, Jose R
AU  - Romero JR
AD  - Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Suzuka, Sandra M
AU  - Suzuka SM
FAU - Nagel, Ronald L
AU  - Nagel RL
FAU - Fabry, Mary E
AU  - Fabry ME
LA  - eng
GR  - 1M01RR12248/RR/NCRR NIH HHS/United States
GR  - DK02817/DK/NIDDK NIH HHS/United States
GR  - P01HL55435/HL/NHLBI NIH HHS/United States
GR  - P60HL38655/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Hemoglobins)
RN  - 0 (Potassium Channels, Calcium-Activated)
RN  - 29VT07BGDA (Citrulline)
RN  - 94ZLA3W45F (Arginine)
RN  - RWP5GA015D (Potassium)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Anemia, Sickle Cell/*drug therapy
MH  - Animals
MH  - Arginine/administration & dosage/blood/*pharmacology
MH  - Citrulline/blood
MH  - Disease Models, Animal
MH  - Erythrocyte Count
MH  - Erythrocytes/cytology/*drug effects
MH  - Hemoglobins/drug effects/metabolism
MH  - Humans
MH  - Kinetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Oxygen/pharmacology
MH  - Potassium/metabolism
MH  - Potassium Channels, Calcium-Activated/*antagonists & inhibitors/metabolism
EDAT- 2002/02/07 10:00
MHDA- 2002/04/26 10:01
CRDT- 2002/02/07 10:00
PHST- 2002/02/07 10:00 [pubmed]
PHST- 2002/04/26 10:01 [medline]
PHST- 2002/02/07 10:00 [entrez]
AID - S0006-4971(20)38199-4 [pii]
AID - 10.1182/blood.v99.4.1103 [doi]
PST - ppublish
SO  - Blood. 2002 Feb 15;99(4):1103-8. doi: 10.1182/blood.v99.4.1103.