scholarly journals Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Explains the “L-Arginine Paradox” and Acts as a Novel Cardiovascular Risk Factor

2004 ◽  
Vol 134 (10) ◽  
pp. 2842S-2847S ◽  
Author(s):  
Rainer H. Böger
Keyword(s):  
Nitric Oxide ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Nitric Oxide Synthase ◽  
Cardiovascular Risk Factor ◽  
Asymmetric Dimethylarginine ◽  
Endogenous Inhibitor ◽  
Oxide Synthase

Effect of asymmetric dimethyl arginine on nitric oxide synthase activity in normal and pre-eclamptic placentae

1995 ◽  
Vol 7 (6) ◽  
pp. 1581 ◽  
Author(s):  
RG King ◽  
Iulio JL Di ◽  
NM Gude ◽  
SP Brennecke
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Asymmetric Dimethylarginine ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Endogenous Inhibitor ◽  
Asymmetric Dimethyl Arginine ◽  
Dimethyl Arginine ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

An endogenous inhibitor of nitric oxide synthase (NOS), NG,NG dimethylarginine (asymmetric dimethylarginine, ADMA), which is present in human plasma and urine, has been reported to be elevated in the plasma of women with pre-eclampsia. As ADMA inhibition may contribute to reduced placental NOS activity observed in pre-eclampsia, the aim of this study was to compare the effects of ADMA on placental NOS activity from pre-eclamptic and normal pregnancies (gestational ages 38.4 +/- 0.9 and 38.3 +/- 0.3 weeks respectively). NOS activity was determined by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in homogenates of normal and pre-eclamptic placentae in the absence and presence of increasing concentrations of ADMA (1-100 microM). The IC50 for ADMA for the pre-eclamptic placentae (22.1 +/- 2.1 microM, n = 6) was not significantly different from that for the normal placentae (18.8 +/- 1.4 microM, n = 6). When ADMA and L-arginine in homogenates was removed by ion exchange chromatography and exogenous L-arginine replaced (32 microM), the IC50 for the pre-eclamptic placentae (19.5 +/- 1.8 microM, n = 6) was not significantly different than that for the normal placentae (20.9 +/- 1.0 microM, n = 6), and NOS activity in the absence of endogenous and exogenous ADMA was still reduced in pre-eclamptic placentae. These results provide no evidence that the sensitivity of placental NOS to ADMA is affected by pre-eclampsia, or that placental ADMA contributes to the reduction of placental NOS in pre-eclampsia.

scholarly journals Plasma Concentration of Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Is Elevated in Monkeys With Hyperhomocyst(e)inemia or Hypercholesterolemia

2000 ◽  
Vol 20 (6) ◽  
pp. 1557-1564 ◽  
Author(s):  
Rainer H. Böger ◽  
Stefanie M. Bode-Böger ◽  
Karsten Sydow ◽  
Donald D. Heistad ◽  
Steven R. Lentz
Keyword(s):  
Nitric Oxide ◽  
Plasma Concentration ◽  
Nitric Oxide Synthase ◽  
Asymmetric Dimethylarginine ◽  
Endogenous Inhibitor ◽  
Oxide Synthase

Impact of Catheter Arteriography on the Serum Level of Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase

2008 ◽  
Vol 31 (3) ◽  
pp. 490-495 ◽  
Author(s):  
Ugur Bozlar ◽  
Mehmet Sahin Ugurel ◽  
Omer Ozcan ◽  
Erdinc Cakir ◽  
Bahri Ustunsoz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Serum Level ◽  
Asymmetric Dimethylarginine ◽  
Endogenous Inhibitor ◽  
Oxide Synthase

Abstract 162: Detection of N-alpha-acetyltransferase Activity Towards Endogenous Inhibitor of Nitric Oxide Synthase Asymmetric Dimethylarginine in the Liver and Kidneys

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Roman N Rodionov ◽  
Dmitrii V Burdin ◽  
Jens Martens-Lobenhoffer ◽  
Silke Brilloff ◽  
Natalia Jarzebska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Asymmetric Dimethylarginine ◽  
Alternative Pathway ◽  
Saline Infusion ◽  
Bilateral Nephrectomy ◽  
Endogenous Inhibitor ◽  
Liver And Kidney ◽  
Oxide Synthase

Background: Endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) has been proposed as a risk factor and mediator of cardiovascular diseases. ADMA can undergo hydrolysis by dimethylarginine dimethylaminohydrolase or be processed through an alternative pathway by alanine:glyoxylate aminotransferase 2. We and other have also shown that ADMA can be N-acetylated to form asymmetrical Nα-acetyldimethylarginine (Ac-ADMA). The goal of the study was to characterize this novel pathway in vivo and identify the organs, which are responsible for the ADMA-acetylating activity. Results: We infused ADMA in mice for three days. Control mice received saline infusion. Half of the mice underwent bilateral nephrectomy 24 hours before completion of the infusion, the rest had a sham surgery. ADMA infusion resulted in a 3.5 fold rise in plasma Ac-ADMA levels in the sham-operated mice (1.35 ± 0.45 nmol/L vs. 4.77 ± 0.88 nmol/L). In nephrectomized mice plasma Ac-ADMA levels were markedly increased even after saline infusion (45.08 ± 9.25 nmol/L) and further raised 5-fold after ADMA infusion (229.65 ± 91.30 nmol/L). We assessed tissue distribution of Ac-ADMA in mice and found the highest levels in pancreas, small intestine, liver and kidney. We incubated the lysates of those organs with ADMA for 24 hours and estimated production of Ac-ADMA. Only liver and kidney lysates showed significant increase in Ac-ADMA levels upon addition of ADMA (from 0.03 ± 0.01 nmol/μg protein to 0.18 ± 0.06 nmol/μg protein and from 0.06 ± 0.01 nmol/μg protein to 0.11 ± 0.02 nmol/μg protein). Conclusions: We showed that overload of ADMA leads to increase in plasma Ac-ADMA levels. This observation is consistent with the hypothesis that Ac-ADMA is formed from ADMA in vivo. The striking rise in plasma Ac-ADMA concentrations after bilateral nephrectomy suggests that Ac-ADMA is predominantly eliminated via the kidneys. We demonstrated that liver and kidney are the organs, in which acetylation of ADMA takes place. The high levels of Ac-ADMA in pancreas and intestine may be due to accumulation of Ac-ADMA in those organs. In the next step we want to identify the enzyme responsible for acetylation of ADMA and explore the clinical implications of this novel pathway of ADMA metabolism.

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