Estrogen replacement therapy lowers plasma levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase

We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension ( n = 9) compared with normal controls ( n = 10). We now test the hypothesis that the patients in this study have increased circulating levels of the cNOS inhibitor, asymmetric dimethylarginine (ADMA), or the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (HODE), which is a marker of reactive oxygen species. Patients had significantly ( P < 0.001) elevated (means ± SD) plasma levels of ADMA (PADMA, 766 ± 217 vs. 393 ± 57 nmol/l) and symmetric dimethylarginine (PSDMA: 644 ± 140 vs. 399 ± 70 nmol/l) but similar levels of l-arginine accompanied by significantly ( P < 0.015) increased rates of renal ADMA excretion (21 ± 9 vs. 14 ± 5 nmol/μmol creatinine) and decreased rates of renal ADMA clearance (18 ± 3 vs. 28 ± 5 ml/min). They had significantly increased plasma levels of HODE (PHODE: 309 ± 30 vs. 226 ± 24 nmol/l) and renal HODE excretion (433 ± 93 vs. 299 ± 67 nmol/μmol creatinine). For the combined group of normal and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly ( P < 0.001) and inversely correlated with microvascular EDRF/NO and positively correlated with mean blood pressure. In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure.

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O35. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, increases the risk of cardiovascular disease and mortality in humans

Nitric Oxide ◽

10.1016/j.niox.2006.04.039 ◽

2006 ◽

Vol 14 (4) ◽

pp. 11

Author(s):

Rainer H. Boger

Keyword(s):

Nitric Oxide ◽

Cardiovascular Disease ◽

Nitric Oxide Synthase ◽

Asymmetric Dimethylarginine ◽

Endogenous Inhibitor ◽

Oxide Synthase

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

Reproduction Fertility and Development ◽

10.1071/rd9951581 ◽

1995 ◽

Vol 7 (6) ◽

pp. 1581 ◽

Cited By ~ 11

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.

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