Medium-term methionine supplementation increases plasma homocysteine but not ADMA and improves blood pressure control in rats fed a diet rich in protein and adequate in folate and choline.
BACKGROUND
Hyperhomocysteinemia (HHcy) is associated with cardiovascular risk, possibly because it increases asymmetric dimethyl-arginine (ADMA), but the general association remains unclear and may vary with nutritional and physiological conditions.


OBJECTIVE
We aimed to monitor the effect of methionine supplementation, and subsequent HHcy, on plasma ADMA and hemodynamics in the context of a diet rich in protein and adequate in folic acid and choline.


METHODS
For 6 weeks, rats were fed a 29% protein diet supplemented (M) or not (C) with 8 g/kg L: -methionine. Blood pressure and plasma amino acids, including homocysteine and ADMA, were measured throughout the experiment and additional parameters, including in vivo hemodynamic response to acetylcholine, were measured at week 5-6.


RESULTS
As compared to the C diet, the M diet induced a marked HHcy during the first 3 weeks, which lessened at week 5. In contrast, plasma ADMA stayed similar in the C and M diet. Paradoxically, M rats had lower mean and diastolic blood pressure values over the experiment, together with a lower left ventricular mass at week 6, when compared with C rats. No difference was observed between groups regarding vascular reactivity and plasma NOx at week 6.


CONCLUSIONS
In a context of a diet rich in protein and adequate in methyl donors, rats exhibit a complex adaptation to the medium-term methionine supplementation, with improvement in blood pressure control despite marked HHcy. The lack of increase in plasma ADMA may account for the absence of detrimental effects of HHcy on hemodynamics.
Mariotti
François
F
UMR INRA-INAPG 914 Physiologie de la, Nutrition et du Comportement Alimentaire, Institut National Agronomique, Paris-Grignon, Paris, France. mariotti@inapg.inra.fr
Hammiche
Alexia
A
Blouet
Clémence
C
Daré
Sophie
S
Tomé
Daniel
D
Huneau
Jean François
JF
D000222:Adaptation, Physiological; D000818:Animals; D019540:Area Under Curve; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002794:Choline / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D019587:Dietary Supplements; D005492:Folic Acid / Q000008:administration & dosage; D006710:Homocysteine / Q000097:blood*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D008745:Methylation; D009569:Nitric Oxide / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004044:Dietary Proteins; D006710:Homocysteine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D005492:Folic Acid; D001120:Arginine; D008715:Methionine; D002794:Choline