Interference ofL-Arginine Analogues withL-Arginine Transport Mediated by the y+Carrier hCAT-2B

Closs, Ellen I.; Basha, Fatima Z.; Habermeier, Alice; Förstermann, Ulrich

doi:10.1006/niox.1996.0106

Cited by 352 publications

(288 citation statements)

References 20 publications

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“…We also reported recently that SDMA is a prospective marker of total mortality after ischemic stroke (19). Several explanations for this observation including increased formation of reactive oxygen species, competition for L-arginine transport into endothelial cells, or valid reflection of renal function by SDMA have been proposed (18,20,21).…”

Section: Introductionmentioning

confidence: 79%

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Schutte¹,

Schutte²,

Huisman³

et al. 2010

European Journal of Endocrinology

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Objective: Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMA's counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk. Since little information regarding ADMA or SDMA is available for Africans, our aim was to explore the relationships of ADMA and SDMA with measures of arterial stiffness and IR in Africans and Caucasians from South Africa. Methods: The study consisted of 235 nonsmoking, nondiabetic, nonobese, human immunodeficiency virus-uninfected Africans (nZ64) and Caucasians (nZ171), aged 20-70 years. We measured blood pressure, pulse wave velocity, ADMA, SDMA, and IR (homeostasis model assessment, HOMA). Results: African and Caucasian men had similar ADMA and SDMA, whereas Caucasian women had higher ADMA and SDMA than African women (P!0.05). African men and Caucasian women indicated strong correlations of ADMA with arterial stiffness (rZ0.47, PZ0.021; rZ0.26, PZ0.008), confirmed in multivariate analyses. Caucasian participants showed negative associations between SDMA and HOMA, being strongest in the men (rZK0.41; PZ0.002). Conclusion: Our results indicate that ADMA is independently associated with vascular dysfunction in African men and Caucasian women. A strong, independent negative association of SDMA with IR was found only in Caucasian participants. The molecular explanation for this is unclear, but these findings motivate experimental studies that could shed more light on these relationships.

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Section: Introductionmentioning

confidence: 79%

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Schutte¹,

Schutte²,

Huisman³

et al. 2010

European Journal of Endocrinology

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“…6C), suggesting a possible role of CAT-2B in the regulation of extracellular L-arginine and CD3 expression. Although L-NMMA can also inhibit iNOS activity, we have used L-SDMA and Llysine, which do not inhibit iNOS at the concentration used (1 mM) (24). In addition, iNOS inhibitors L-NIL, L-NNA, and L-NAME, which are not transported by CAT-2B failed to recover CD3 expression after T cell stimulation.…”

Section: Discussionmentioning

confidence: 99%

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Rodríguez

Zea

DeSalvo

et al. 2003

The Journal of Immunology

417

354

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l-Arginine plays a central role in the normal function of several organs including the immune system. It is metabolized in macrophages by inducible nitric oxide synthase to produce nitric oxide, important in the cytotoxic mechanisms, and by arginase I (ASE I) and arginase II (ASE II) to synthesize l-ornithine and urea, the first being the precursor for the production of polyamines needed for cell proliferation. l-Arginine availability can modulate T cell function. Human T cells stimulated and cultured in the absence of l-arginine lose the expression of the TCR ζ-chain (CD3ζ) and have an impaired proliferation and a decreased cytokine production. The aim of this work was to test whether activated macrophages could modulate extracellular levels of l-arginine and alter T cell function, and to determine which metabolic pathway was responsible for this event. The results show that macrophages stimulated with IL-4 + IL-13 up-regulate ASE I and cationic amino acid transporter 2B, causing a rapid reduction of extracellular levels of l-arginine and inducing decreased expression of CD3ζ and diminished proliferation in normal T lymphocytes. Competitive inhibitors of ASE I or the addition of excess l-arginine lead to the re-expression of CD3ζ and recovery of T cell proliferation. In contrast, inducible nitric oxide synthase or ASE II failed to significantly reduce the extracellular levels of l-arginine and modulate CD3ζ expression. These results may provide new insights into the mechanisms leading to T cell dysfunction and the down-regulation of CD3ζ in cancer and chronic infectious diseases.

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“…11 Symmetric dimethylarginine (SDMA) does not inhibit endothelial NO synthase, but it interferes with Larginine uptake via the y þ carrier into the endothelial cells. 12 Both ADMA and SDMA are risk markers for vascular disease, 13 --18 while SDMA is also reported to predict renal damage. 19 L-arginine supplementation improves the reduced vasodilatory response in offspring of hypertensive patients and in normotensive patients with familial essential hypertensive histories, suggesting that a genetic predisposition to essential hypertension involves a defect in NO generation.…”

Section: Introductionmentioning

confidence: 99%

Ethnicity-specific differences in L-arginine status in South African men

et al. 2011

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The aetiology for an increasing incidence of hypertensive cardiovascular disease amongst Africans in southern Africa is unclear. Hypertension may be induced by inadequate release of L-arginine-derived nitric oxide impairing vascular tone regulation. In addition, asymmetric dimethylarginine (ADMA) is associated with cardiovascular disease. We compared profiles of L-arginine in African and Caucasian men of similar age with cardiovascular risk factors. We studied 163 Caucasian and 132 African men, respectively, (20 to 70 years) measuring serum L-arginine, ADMA, creatinine, urea, symmetric dimethylarginine (SDMA) and blood pressure. L-arginine levels were significantly lower, whereas blood pressure and pulse wave velocity were significantly higher in African men. Simple linear regression showed ADMA more strongly associated with L-arginine in Caucasians (r ¼ 0.59 vs 0.19), whereas association of SDMA with L-arginine was significant only in Caucasians (r ¼ 0.43 vs 0.001). The stronger association of L-arginine with ADMA in Caucasian men was confirmed by multiple regression analysis (b ¼ 0.46 vs 0.25). Our findings show that the relationship of cardiovascular risk factors with serum L-arginine and some of its catabolites is different in African and Caucasian men and that this may be associated with a relatively higher prevalence of hypertension in African men.

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Interference ofL-Arginine Analogues withL-Arginine Transport Mediated by the y+Carrier hCAT-2B

Cited by 352 publications

References 20 publications

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Ethnicity-specific differences in L-arginine status in South African men

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