Nitrogen Metabolism in Sickle Cell Anemia: Free Amino Acids in Plasma and Urine

Enwonwu, Cyril O.; Xu, Xu-Xiang; Turner, Edward L.

doi:10.1097/00000441-199012000-00005

Cited by 63 publications

(28 citation statements)

References 23 publications

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“…For comparison, humans homozygous for hemoglobin A have 78.2 Ϯ 6.4 mol per liter versus 48.6 Ϯ 3.8 mol per liter for patients with homozygous hemoglobin S, which makes the decrease in mice larger than that seen in humans with sickle cell disease. 6 The 5% arginine diet restored the plasma arginine level to that found in C57BL mice. The ratio of citrulline to glycine was also measured: C57BL, regular chow 0.21 Ϯ 0.03; SϩS-Antilles, regular chow 0.17 Ϯ 0.03; and SϩS-Antilles, 5% arginine 0.25 Ϯ 0.01 (P Ͻ .002, SϩS-Antilles-off diet vs SϩS-Antilles-on diet).…”

Section: Plasma Arginine Is Decreased In S؉s-antilles Micementioning

confidence: 82%

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

Romero

Suzuka

Nagel

et al. 2002

Blood

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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 ␣, human ␤ S , and human ␤ S-Antilles and is homozygous for the mouse ␤ major deletion (S؉S-Antilles). S؉S-Antilles mice were supplemented with a 4-fold increase in arginine that was maintained for several months.

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Section: Plasma Arginine Is Decreased In S؉s-antilles Micementioning

confidence: 82%

“…Arginine depletion has been reported in sickle cell patients [5][6][7] and may be related to increased NOS activity. Arginine is a nonessential amino acid that can be synthesized from citrulline and other sources; however, it can be depleted either globally or locally.…”

Section: Introductionmentioning

confidence: 99%

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

Romero

Suzuka

Nagel

et al. 2002

Blood

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“…The observation that patients with sickle cell anemia have significantly reduced concentrations of arginine in their plasma and urine suggests that this group of patients may have increased use or catabolism of this key substrate of NO biosynthesis, and therefore increased nutritional requirements (177,178). Indeed, L-arginine levels are depressed in patients with sickle cell disease, particularly during vaso-occlusive pain crisis and during acute chest syndrome (179).…”

Section: Therapeutic Strategies Aimed To Increase Nitric Oxide Bioavamentioning

confidence: 99%

Redox-dependent impairment of vascular function in sickle cell disease

Aslan

Freeman

2007

Free Radical Biology and Medicine

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The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors including adhesiveness of red and white blood cells to endothelium, increased coagulation and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. Occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory and oxidative abnormalities may reduce the frequency of hospitalization, blood transfusion, the incidence of pain and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.

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“…Although some studies have suggested that these levels are high in patients with sickle cell disease, 4 others find that NOx levels and L-arginine are depressed, particularly during vasoocclusive crisis and the acute chest syndrome, and that these levels vary inversely with pain symptomatology. [5][6][7][8] Such studies are limited by confounding effects of illness, diet, and renal function. Endothelial function studies from transgenic sickle cell mice and humans provide similarly conflicting data.…”

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confidence: 99%

Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease

et al. 2003

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Background-Although reduced endothelial nitric oxide (NO) bioavailability has been demonstrated in arteriosclerotic vascular disease, the integrity of this system in sickle cell disease remains uncertain. Methods and Results-We measured forearm blood flow in 21 patients with sickle cell disease (hemoglobin SS genotype) and 18 black control subjects before and after intra-arterial infusions of acetylcholine, nitroprusside, and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Endothelium-dependent vasodilation, measured by the percent increase in flow induced by acetylcholine infusion, was significantly greater than in controls (252Ϯ37% for patients versus 134Ϯ24% for controls; PϽ0.0001). However, there was a large sex difference in blood flow responses between female and male patients (340Ϯ46% versus 173Ϯ41%; Pϭ0.035). Similarly, basal NO bioactivity, as measured by the percent decrease in flow induced by L-NMMA, was depressed in male compared with female patients (Ϫ17Ϯ5% versus Ϫ34Ϯ4%; Pϭ0.01), as was the response to nitroprusside (86Ϯ21% versus 171Ϯ22%; Pϭ0.008). L-NMMA reduced the blood flow response to acetylcholine in women, but not in men. Sex differences in vascular cell adhesion molecule-1 were appreciated, with significant correlations between levels of soluble vascular cell adhesion molecule-1 and blood flow responses to L-NMMA and nitroprusside (rϭ0.53, Pϭ0.004 and rϭϪ0.66, PϽ0.001, respectively). Conclusions-NO bioavailability and NO responsiveness are greater in women than in men with sickle cell disease and determines adhesion molecule expression. Endothelium-dependent blood flows are largely non-NO mediated in male patients. These results provide a possible mechanism for reported sex differences in sickle cell disease morbidity and mortality and provide a basis for novel pharmacological interventions.

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Nitrogen Metabolism in Sickle Cell Anemia: Free Amino Acids in Plasma and Urine

Cited by 63 publications

References 23 publications

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

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

Redox-dependent impairment of vascular function in sickle cell disease

Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease

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