title: Chronic mild hyperhomocysteinemia induces aortic endothelial dysfunction but does not elevate arterial pressure in rats.
abstract: Mild hyperhomocysteinemia is prevalent in the general population and has been linked to endothelial dysfunction and high arterial pressure (AP) in clinical studies. The present study was designed to determine whether a rise in AP was induced by mild hyperhomocysteinemia and whether the potential rise in AP is secondary or prior to endothelial dysfunction. Experiments were performed in a rat model of mild hyperhomocysteinemia induced by oral administration of homocysteine for 1-4 months. Aortic endothelial dysfunction was observed 2 months after homocysteine treatment while endothelium-independent vasodilation was normal. In parallel, homocysteine treatment increased phenylephrine-induced contraction in aortas with endothelium, but did not modify the contraction in aortas without endothelium, suggesting a decrease of basal NO production. In conscious unrestrained rats, AP was not significantly different 1, 2, 3 and 4 months after homocysteine treatment. In correlation, endothelial function of a resistance vessel (mesenteric artery), mainly non-NO nonprostanoid factor mediated, was preserved, indicating that homocysteine treatment only affected the NO pathway. In conclusion, mild hyperhomocysteinemia alone is not sufficient to elevate arterial blood pressure, at least in the rat model. Aortic endothelial dysfunction produced by mild hyperhomocysteinemia is independent of hemodynamic factors.
authors.affiliation: Cardiovascular Research Division, SERVIER Research Institute, FR-92150 Suresnes, France.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
authors.forename: Nicole
authors.initials: N
authors.lastname: Villeneuve
authors.forename: Christine
authors.initials: C
authors.lastname: Brunel-Jacquemin
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Guillaumin
authors.forename: Denis
authors.initials: D
authors.lastname: Gransagne
authors.forename: Cyril
authors.initials: C
authors.lastname: Briant
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vilaine
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001794:Blood Pressure; D001835:Body Weight; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D006710:Homocysteine / Q000008:administration & dosage / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D006710:Homocysteine