Asymmetric and symmetric dimethylarginines are of similar predictive value for cardiovascular risk in the general population

Kiechl, Stefan; Lee, Terry; Santer, Peter; Thompson, G M; Tsimikas, Sotirios; Egger, Georg; Holt, David W.; Willeit, Johann; Xu, Qingbo; Mayr, Manuel

doi:10.1016/j.atherosclerosis.2008.10.040

Cited by 65 publications

(70 citation statements)

References 25 publications

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“…The results of our analysis are consistent with previously described interactions of these mechanisms in an epidemiological context. 19,29,33,58,59 In addition, our results contribute to an understanding of the metabolic role of L-arginine in the differential prevalence of hypertension in Africans and Caucasians.…”

Section: Discussionmentioning

confidence: 69%

“…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. 9 Various aspects of the effect of L-arginine augmentation have been studied in human subjects, 20 --22 in animal experiments 23,24 and in tissue culture.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…Thus, this structural isomer was thought to be inert (18) and it has not been evaluated in most studies focusing on cardiovascular disease (8). However, recent publications suggest that SDMA has a similar predictive value for cardiovascular risk than ADMA (8).…”

Section: Introductionmentioning

confidence: 99%

“…ADMA, which is regarded as the predominant endogenous nitric oxide (NO) synthase inhibitor (9), is found in all human tissues and biological fluids, and is generated by the post-translational methylation of arginine residues in proteins (8). Owing to its inhibitory effect on NO synthase, ADMA has been implicated in the impairment of NO generation in a variety of cardiovascular diseases (16).…”

Section: Introductionmentioning

confidence: 99%

“…In Caucasian populations, elevated concentrations of asymmetric dimethylarginine (ADMA) have consistently been associated with cardiovascular disease (8)(9)(10)(11)(12) and insulin resistance (IR) (13)(14)(15). ADMA, which is regarded as the predominant endogenous nitric oxide (NO) synthase inhibitor (9), is found in all human tissues and biological fluids, and is generated by the post-translational methylation of arginine residues in proteins (8).…”

Section: Introductionmentioning

confidence: 99%

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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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Measurement of Arginine Metabolites: Regulators of Nitric Oxide Metabolism

Augustine

Rogers

2013

CP Toxicology

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Arginine is the substrate for nitric oxide synthases (NOS), and arginine availability regulates the production of nitric oxide. Through the activity of methyltransferases, arginine can be methylated to form monomethylarginine (NMMA), asymmetrical dimethylarginine (ADMA), and symmetrical dimethylarginine (SDMA). NMMA and ADMA directly inhibit NOS, whereas SDMA inhibits the cellular import of arginine through the cationic amino acid transporter. Increased levels of methylarginine compounds have been associated with many diseases including atherosclerosis, renal failure, pulmonary hypertension, and preeclampsia. Previous HPLC methods to measure these molecules rely on derivatization with ortho-phthalaldehyde, which is unstable and requires immediate pre- or post-column reactions. We have identified a new fluorometric agent that is stable for at least 1 week and provides chromatographic properties that facilitate separation of these chemically similar compounds by reverse phase chromatography.

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Asymmetric and symmetric dimethylarginines are of similar predictive value for cardiovascular risk in the general population

Cited by 65 publications

References 25 publications

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

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

Dimethylarginines: their vascular and metabolic roles in Africans and Caucasians

Measurement of Arginine Metabolites: Regulators of Nitric Oxide Metabolism

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