Quantitative spectrophotometric determination of human and rat urinary dimethylamine

Beal, Diane D.; Bryan, George T.

doi:10.1016/0006-2944(78)90038-8

Cited by 7 publications

(2 citation statements)

References 19 publications

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“…The present study shows a substantial increase in urinary dimethylamine excretion after administration of ADMA and is the first demonstration of DDAH activity in humans in vivo. The bulk of urinary dimethylamine (260 mol/d, as shown in this study and previous studies 13,28 ) is thought to arise from an endogenous source, 29 suggesting that the rate of ADMA metabolism is in the order of 130 to 260 mol/d compared with a renal excretion rate of approximately 60 mol/d. 2 Consistent with these estimates, the average protein turnover is approximately 300 g/d and the average ADMA content is approximately 1 to 2 mol/g protein, 30 giving a total body production of 300 mol ADMA in 24 hours.…”

Section: Achan Et Al Hemodynamic Effects and Fate Of Adma In Humans 1457mentioning

confidence: 87%

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Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase

Achan

Broadhead

Malaki

et al. 2003

ATVB

542

394

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Objective-Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure, hypertension, and chronic heart failure. In patients with renal failure, plasma ADMA levels are an independent correlate of left ventricular ejection fraction. However, the cardiovascular effects of a systemic increase in ADMA in humans are not known. Methods and Results-In a randomized, double-blind, placebo-controlled study in 12 healthy male volunteers, we compared the effects of intravenous low-dose ADMA and placebo on heart rate, blood pressure, cardiac output, and systemic vascular resistance at rest and during exercise. We also tested the hypothesis that ADMA is metabolized in humans in vivo by dimethylarginine dimethylaminohydrolase (DDAH) enzymes. Low-dose ADMA reduced heart rate by 9.2Ϯ1.4% from 58.9Ϯ2.0 bpm (PϽ0.001) and cardiac output by 14.8Ϯ1.2% from 4.4Ϯ0.3 L/min (PϽ0.001).ADMA also increased mean blood pressure by 6.0Ϯ1.2% from 88.6Ϯ3.4 mm Hg (PϽ0.005) and SVR by 23.7Ϯ2.1% from 1639.0Ϯ91.6 dyne · s · cm Ϫ5 (PϽ0.001). Handgrip exercise increased cardiac output in control subjects by 96.8Ϯ23.3%, but in subjects given ADMA, cardiac output increased by only 35.3Ϯ10.6% (PϽ0.05). DDAHs metabolize ADMA to citrulline and dimethylamine. Urinary dimethylamine to creatinine ratios significantly increased from 1.26Ϯ0.32 to 2.73Ϯ0.59 after ADMA injection (PϽ0.01). We estimate that humans generate approximately 300 mol of ADMA per day, of which approximately 250 mol is metabolized by DDAHs. Conclusions-This study defines the cardiovascular effects of a systemic increase in ADMA in humans. These are similar to changes seen in diseases associated with ADMA accumulation. Finally, our data also indicate that ADMA is metabolized by DDAHs extensively in humans in vivo. Key Words: asymmetric methylarginine Ⅲ dimethylarginine dimethylaminohydrolase Ⅲ nitric oxide Ⅲ hypertension Ⅲ cardiac output N itric oxide (NO) plays an important role in the regulation of cardiovascular function, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, has been implicated in the impairment of NO generation in a variety of cardiovascular diseases. 1 The finding that plasma ADMA levels are elevated in chronic renal failure led to speculation that ADMA may in part be responsible for increased cardiovascular risk and hypertension in these patients. 2 Subsequent studies have shown strong associations between raised ADMA levels and cardiovascular risk factors, endothelial dysfunction, hypertension, atherosclerosis, and cardiovascular mortality. 3-7 ADMA levels are also significantly raised in patients with chronic heart failure, 8 rats with heart failure induced by coronary artery ligation, 9 and dogs with heart failure induced by rapid pacing. 10 A recent analysis of a large group of patients with end-stage renal failure demonstrated an inverse relationship between ADMA levels and left ventricular (LV) ejection fraction; in a multivariate analysis that included L...

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Section: Achan Et Al Hemodynamic Effects and Fate Of Adma In Humans 1457mentioning

confidence: 87%

“…2 Dimethylamine levels in the urine (mol/L) were determined by the method of Beal and Bryan. 13 Urinary creatinine (Cr) levels (mg/dL) were measured using a modification of the method of Slot. 14 …”

Section: Biochemical Measurementsmentioning

confidence: 99%

Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase

Achan

Broadhead

Malaki

et al. 2003

ATVB

542

394

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Novel Flow‐through Potentiometric System for Dimethyamine Assessment Using New Ion Exchangers Doped‐polymeric Membrane Sensors

2018

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New simple potentiometric sensing systems are described for the sensitive and selective monitoring of dimethylamine (DMA). These systems are based on using polymeric membranes doped in some ion exchangers such as dimethylamine/phosphomolybdate [(CH3)2NH3]22+[MP]2− (Sensor I), dimethylamine/tetraphenylborate [(CH3)2NH3]+[TPB]− (Sensor II) and dimethylamine/phosphotungstate [(CH3)2NH3]+[TP]− (sensor III). All the sensing systems are incorporated in poly(vinyl chloride) matrix plasticized with o‐NPOE. In a Trizma buffer solution of pH 7.1, the sensors exhibit a stable, fast and linear response for 5.0×10−6–1.0×10−2, 2.5×10−5–1.0×10−2, and 5.0×10−6–1.0×10−2 mol L−1 DMA+ with slopes of 53.2±0.4, 49.4±0.6, and 53.8±0.3 mV decade−1, and detection limits of 2.0×10−6 (0.16 μg mL−1), 1.6×10−5(1.3 μg mL−1), and 1.4×10−6 (0.11 μg mL−1) mol L−1 for sensors (I), (II), and (III), respectively. Potentiometric selectivity measurements of these sensors reveal negligible interferences from most common aliphatic and aromatic amines. Satisfactory results are obtained with an average accuracy of 99.5 % and a mean precision of ±0.5 %. Validation of the proposed assay methods are examined by measuring the limit of detection, linearity range, accuracy, precision, within‐day repeatability, between‐days reproducibility and method ruggedness. Good performance characteristics and applicability of these sensors for DMA assessment in different matrices under static and hydrodynamic modes of measurements are demonstrated. The proposed sensors are also prepared in a tubular form and used as DMA detector in a two‐channel flow injection setup for continuous monitoring. The frequency rate is 27–53 samples h−1. The sensors are satisfactory applied for DMA quantification in both biological matrices and environmental samples with recoveries ranging between 95.0 and 104.0 %.

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N G ,N G -Dimethyl-l-arginine, a dominant precursor of endogenous dimethylamine in rats

1994

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The metabolic significance ofN (G) ,N (G) -dimethyl-L-arginine (DMA) as a precursor of endogenous dimethylamine (DMN) in rats was examined in connection with the wide distribution and active operation of dimethylargininase (EC3.5.3.18) in rat tissues (Kimoto et al., 1993). When [methyl-(14)C]DMA was administered intraperitoneally to rats, the radioactive DMN was detected in various tissues as a major radioactive metabolite one hour after injection, and about 65% of the radioactivity administered was recovered in the first 12-h urine as DMN. In the case of the [(14)C] DMN-injected rats, almost all the radioactivity was excreted in the 12-h urine as DMN, except for a negligible amount of radioactivity found in urea. The time-dependent decrease in the specific radioactivity of DMA and DMN in urine showed that dimethylargininase was significantly involved in thein vivo formation of DMN by the hydrolytic cleavage of DMA released from methylated proteins and that DMA is a dominant precursor of endogenous DMN in rats.

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Quantitative spectrophotometric determination of human and rat urinary dimethylamine

Cited by 7 publications

References 19 publications

Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase

Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase

Novel Flow‐through Potentiometric System for Dimethyamine Assessment Using New Ion Exchangers Doped‐polymeric Membrane Sensors

N G ,N G -Dimethyl-l-arginine, a dominant precursor of endogenous dimethylamine in rats

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