Diet-induced mild hyperhomocysteinemia and increased salt intake diminish vascular endothelial function in a synergistic manner.
OBJECTIVE
We investigated the influence of hyperhomocysteinemia and high salt intake on sodium handling, oxidative state, vascular endothelial function and blood pressure in a rat model.


METHODS
Eight-week-old male Sprague-Dawley rats were divided into subgroups and maintained for 4 weeks prior to experimentation on either control chow containing 0.36% methionine and 0.5% NaCl; or one of the following modified diets containing either 0.7% methionine, 8% NaCl or 0.7% methionine + 8% NaCl. Sodium handling, homocysteine metabolism, lipid profile, NO synthesis, oxidative state, blood pressure and relaxation to acetylcholine of carotid rings were evaluated and compared.


RESULTS
Diet-induced mild hyperhomocysteinemia (plasma homocysteine levels 1.4-fold higher than control), by itself, had no significant influence on sodium excretion, vascular endothelial function and blood pressure. Increased salt intake had no influence on homocysteine metabolism, vascular endothelial function and blood pressure. The coexistence of mild hyperhomocysteinemia and high salt intake significantly diminished vascular endothelial function (rmax to acetylcholine; control chow 83.2 +/- 6.2%, 0.7% methionine diet 74.7 +/- 3.9%, 8% NaCl diet 85.1 +/- 4.6%, 0.7% methionine + 8% NaCl diet 57.9 +/- 6.6%) but manifested no rise in blood pressure. No significant difference in oxidative state was observed in this analysis.


CONCLUSIONS
Diet-induced mild hyperhomocysteinemia, the extent of which is comparable with the levels that are associated with a predisposition to common atherosclerotic diseases, was found to induce vascular endothelial dysfunction only when accompanied by high salt intake.
Morita
Hiroyuki
H
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hmrt-tky@umin.ac.jp
Saito
Yuichiro
Y
Kurabayashi
Masahiko
M
Nagai
Ryozo
R
D000109:Acetylcholine / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005492:Folic Acid / Q000097:blood / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006710:Homocysteine / Q000097:blood / Q000187:drug effects; D020138:Hyperhomocysteinemia / Q000209:etiology*; D007564:Japan; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000009:adverse effects; D009318:Natriuresis / Q000187:drug effects; D009573:Nitrites / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects*
D001786:Blood Glucose; D008055:Lipids; D009573:Nitrites; D017673:Sodium Chloride, Dietary; D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine; D000109:Acetylcholine