Nitric oxide (NO) is produced from arginine by nitric oxide synthase (NOS) and is essential to the maintenance of vascular tone. Plasma arginine levels are reduced in sickle cell anemia patients, and we have previously reported that S+S− Antilles mice have lower plasma arginine than control mice (C57BL). Long term arginine supplementation (5% arginine in chow) restored plasma arginine levels in S+S− Antilles mice to that found in C57BL mice, and, in S+S− Antilles mice, MCHC and the percent high density red cells were reduced. Our observation that Ca++-activated K+ channel [K(Ca) channel or Gardos channel] activity is reduced in supplemented vs non-supplemented S+S− Antilles mice can account for reduced red cell density and dense cell formation (
). The time course of arginine induced changes in red cell indices in sickle transgenic mice has not yet been studied. Using the Advia 120 Hematology System, we found that, within 7 days after the onset of arginine supplementation, MCHC* (CHCM in the Advia system) fell from 33.4±0.5 g/dL to 31.0±0.2 (mean ±SD, P<0.000002, N=6) and the percent high density red cells (MCHC>37 g/dL) decreased from 10.5±4.3 % to 4.5±1.6 (P<0.01, N=6). MCV rose from 43.6±0.8 fL to 46.4±0.5 (P<0.00003, N=6). Reticulocyte counts and mean corpuscular hemoglobin did not vary significantly. Although plasma arginine levels increase within a few hours of oral administration and persist for only a few hours, no change in red cell indices was observed 7 days after discontinuing arginine supplementation, and the indices slowly returned to baseline levels after 40 days. In summary, MCHC* and the percent high density RBCs decrease significantly within 7 days of the onset of arginine supplementation. When arginine supplementation is withdrawn, the return to baseline values is much slower and required more than 40 days to complete. These observations have important implications for arginine supplementation in sickle cell anemia patients. In particular, the persistence of decreased MCHC* and reduced percent high density RBCs for an extended period of time after supplementation was withdrawn parallels our previously reported observation of persistent improvement of perfusion in sickle transgenic mice after supplementation was withdrawn and suggests that daily administration of arginine may not be necessary once an induction period has passed.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal