Plasma asymmetric and symmetric dimethylarginine in a rat model of endothelial dysfunction induced by acute hyperhomocysteinemia.
Level 5 - mechanism / opinion, no new human data
Non-clinical animal experiment
PubMed 25792109 · doi:10.1007/s00726-015-1959-4
What was done
In healthy rats, researchers induced acute hyperhomocysteinemia via methionine loading versus vehicle. Endothelium-related vascular reactivity (acetylcholine-induced transient decrease in mean arterial blood pressure), total plasma homocysteine (tHcy), cysteine, glutathione, and plasma asymmetric (ADMA) and symmetric (SDMA) dimethylarginine were measured before and at 2, 4, and 6 hours post-treatment. Hepatic mRNA expression of dimethylarginine dimethylaminohydrolase-1 (DDAH1), cathepsin D, and ubiquitin was assessed at 6 hours.
What was found
Methionine loading induced a sustained rise in tHcy (up to 54.9 ± 1.9 µM) and a 30% decrease in vascular reactivity relative to baseline. Plasma ADMA and SDMA decreased transiently following methionine loading. Hepatic mRNA expression of DDAH1, cathepsin D, and ubiquitin was significantly lower at 6 hours compared to vehicle.
Why it matters
The findings demonstrate that acute hyperhomocysteinemia-induced endothelial dysfunction occurs without an elevation in circulating ADMA or SDMA, suggesting that methylarginine accumulation is not the driver of vascular impairment in this acute setting.
Limits
The study was conducted in a rat model with acute methionine loading, which may not reflect chronic human pathophysiology. The abstract does not report sample sizes (n) and relies on mRNA expression rather than direct enzyme activity or protein levels.
Cited by
- contradicts Elevated homocysteine impairs the clearance of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA).