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Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading

Wanby, P; Brattstrom, L; Brudin, L; Hultberg, Björn LU and Teerlink, T (2003) In Scandinavian Journal of Clinical & Laboratory Investigation 63(5). p.347-353
Abstract
Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects.... (More)
Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. Methods: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). Results: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 mumol/L, mean +/-SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 mumol/L, both p < 0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 &PLUSMN; 5.9 and 0.66 &PLUSMN; 0.10 μmol/L, both p < 0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 mumol/L, both p < 0.001). However, the corresponding ADMA levels did not increase (0.73 &PLUSMN; 0.17 and 0.76 &PLUSMN; 0.22 vs. 0.70 &PLUSMN; 0.10 μmol/L, both not significant). Conclusions: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
renal function, nitric oxide, endothelium, atherosclerosis, cardiovascular diseases, risk factors
in
Scandinavian Journal of Clinical & Laboratory Investigation
volume
63
issue
5
pages
347 - 353
publisher
Informa Healthcare
external identifiers
  • wos:000185850400005
  • pmid:14599157
  • scopus:0142062109
ISSN
1502-7686
DOI
10.1080/00365510310002040
language
English
LU publication?
yes
id
60f3eea1-ff60-4f6e-a1a5-6797c711a927 (old id 298239)
date added to LUP
2007-09-24 07:12:52
date last changed
2017-01-01 07:27:21
@article{60f3eea1-ff60-4f6e-a1a5-6797c711a927,
  abstract     = {Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. Methods: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). Results: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 mumol/L, mean +/-SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 mumol/L, both p &lt; 0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 &amp;PLUSMN; 5.9 and 0.66 &amp;PLUSMN; 0.10 μmol/L, both p &lt; 0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 mumol/L, both p &lt; 0.001). However, the corresponding ADMA levels did not increase (0.73 &amp;PLUSMN; 0.17 and 0.76 &amp;PLUSMN; 0.22 vs. 0.70 &amp;PLUSMN; 0.10 μmol/L, both not significant). Conclusions: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions.},
  author       = {Wanby, P and Brattstrom, L and Brudin, L and Hultberg, Björn and Teerlink, T},
  issn         = {1502-7686},
  keyword      = {renal function,nitric oxide,endothelium,atherosclerosis,cardiovascular diseases,risk factors},
  language     = {eng},
  number       = {5},
  pages        = {347--353},
  publisher    = {Informa Healthcare},
  series       = {Scandinavian Journal of Clinical & Laboratory Investigation},
  title        = {Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading},
  url          = {http://dx.doi.org/10.1080/00365510310002040},
  volume       = {63},
  year         = {2003},
}