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Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine.

Holden, DP; Cartwright, JE; Nussey, SS; Whitley, GS (2003) Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine. CIRCULATION, 108 (13). 1575 - 1580 (6). ISSN 0009-7322 https://doi.org/10.1161/01.CIR.0000091083.61609.DF
SGUL Authors: Cartwright, Judith Eleanor Whitley, Guy St John

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Abstract

Background— Experimental evidence suggests that estrogens stimulate the production of nitric oxide (NO) by vascular endothelial cells. This effect has been attributed to increased expression and enzymatic activity of both the constitutive and inducible isoforms of NO synthase. In this study, we have investigated whether estrogens regulate the metabolism or release of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. Methods and Results— The concentration of ADMA in the plasma of 15 postmenopausal women was 0.722±0.04 μmol/L (mean±SEM). Two weeks after subcutaneous implantation with estradiol, there was an increase in plasma estradiol concentration from 0.693±0.075 to 0.81±87 nmol/L, which was accompanied by a significant fall in plasma ADMA concentration to 0.588±0.03 μmol/L (P=0.006). Human and murine endothelial cell lines previously cultured in estrogen-free medium and then exposed to 17β-estradiol showed a dose-dependent decrease in the release of ADMA. This reached statistical significance at 10−14 mol/L 17β-estradiol and was accompanied by a corresponding increase in the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catalyzes the metabolism of ADMA. Conclusions— We have demonstrated that estrogens can alter the catabolism and release of ADMA in vitro and reduce the circulating concentration in vivo. We therefore propose that increased DDAH activity and the subsequent fall in ADMA could contribute to the positive effect of estrogen on NO synthesis.

Item Type: Article
Additional Information: PubMed ID: 12963642
Keywords: Amidohydrolases, Arginine, Cardiotonic Agents, Cell Line, Drug Implants, Endothelium, Vascular, Enzyme Activation, Estradiol, Female, Humans, Middle Aged, Postmenopause, Receptors, Estrogen, Tamoxifen, Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Peripheral Vascular Disease, Cardiovascular System & Cardiology, endothelium, nitric oxide, cardiovascular diseases, asymmetric dimethylarginine, NITRIC-OXIDE SYNTHESIS, HEALTHY POSTMENOPAUSAL WOMEN, HUMAN ENDOTHELIAL-CELLS, L-ARGININE, CARDIOVASCULAR-SYSTEM, ENDOGENOUS INHIBITOR, REPLACEMENT THERAPY, PLUS PROGESTIN, PLASMA-LEVELS, SYNTHASE, endothelium, nitric oxide, cardiovascular diseases, asymmetric dimethylarginine
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: CIRCULATION
ISSN: 0009-7322
Related URLs:
Dates:
DateEvent
30 September 2003Published
Web of Science ID: WOS:000185624500022
URI: http://openaccess.sgul.ac.uk/id/eprint/101016
Publisher's version: https://doi.org/10.1161/01.CIR.0000091083.61609.DF

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