Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase
Top Cited Papers
Open Access
- 1 August 2003
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 23 (8), 1455-1459
- https://doi.org/10.1161/01.atv.0000081742.92006.59
Abstract
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 9.2±1.4% from 58.9±2.0 bpm ( P P P −5 ( P P P 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.Keywords
This publication has 25 references indexed in Scilit:
- Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patientsKidney International, 2002
- Elevation of an endogenous inhibitor of nitric oxide synthesis in experimental congestive heart failureCardiovascular Research, 1998
- Pharmacokinetics, disposition and metabolism of 546C88 (L-NG-methylarginine hydrochloride) in rat and dogXenobiotica, 1997
- Fate of dimethylamine in manXenobiotica, 1994
- L-NMMA Increases blood pressure in manThe Lancet, 1993
- Synthesis of NG, NGDimethylarginine by Human Endothelial CellsEndothelium, 1993
- Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failureThe Lancet, 1992
- Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shockThe Lancet, 1991
- Occurrence of a new enzyme catalyzing the direct conversion of NG,NG-dimethyl-L-arginine to L-citrulline in ratsBiochemical and Biophysical Research Communications, 1987
- METHYLATED AMINO ACID RESIDUES OF PROTEINS OF BRAIN AND OTHER ORGANSJournal of Neurochemistry, 1975