title: Acute hyperhomocysteinemia decreases NO bioavailability in healthy adults.
abstract: Hyperhomocysteinemia is associated with decreased vascular reactivity and increased cardiovascular morbidity. Oxidative stress and reduced NO bioavailability have been proposed as a mechanism for the adverse effects of chronically elevated plasma homocysteine levels. Recent studies suggest that acute elevations of plasma homocysteine may also impair endothelial function and vasodilation, however, the mechanism is not clear. In the present study, we investigated whether moderate hyperhomocysteinemia after methionine loading decreases NO bioavailability, increases oxidative stress, and impairs receptor-mediated NO-dependent venodilation in healthy adults. After oral methionine loading (0.1g/kg), mean homocysteine concentrations increased 3.2-fold, from 6.9 +/- 0.5 to 27.8 +/- 1.9 micromol/l (n = 16), whereas plasma NO(x) concentrations, an indicator of NO release, were decreased by 12% compared to placebo treatment (P = 0.005). Vitamin E levels in freshly isolated low density lipoprotein (LDL), a sensitive marker of LDL oxidation, and LDL lipid (hydro)peroxide levels were unchanged after methionine loading. Endothelium-dependent venodilation induced by bradykinin was reduced by 18% during hyperhomocysteinemia (P = 0.06). Taken together our data suggest that the reduced NO bioavailability was likely due to decreased NO synthesis and release rather than to NO destruction by oxidative stress.
authors.affiliation: Department of Internal Medicine, University Hospital Liestal, Kantonsspital Liestal, Rheinstrasse 26, CH-4410 Liestal, Switzerland. silvana.romerio@ksli.ch
authors.forename: Silvana C
authors.initials: SC
authors.lastname: Romerio
authors.forename: Lilly
authors.initials: L
authors.lastname: Linder
authors.forename: Jürg
authors.initials: J
authors.lastname: Nyfeler
authors.forename: Markus
authors.initials: M
authors.lastname: Wenk
authors.forename: Piotr
authors.initials: P
authors.lastname: Litynsky
authors.forename: Reto
authors.initials: R
authors.lastname: Asmis
authors.forename: Walter E
authors.initials: WE
authors.lastname: Haefeli
mesh_terms: D000328:Adult; D001682:Biological Availability; D005260:Female; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
chemical_list: D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D006710:Homocysteine; D009569:Nitric Oxide; D005979:Glutathione Peroxidase