title: Effects of acute hyperhomocysteinemia on the neurovascular coupling mechanism in healthy young adults.
abstract: OBJECTIVE
  Hyperhomocysteinemia is a vascular risk factor that infers with the nitric oxide signaling pathway of endothelial vasoregulation. Most investigations in young healthy humans on the peripheral vasculature using a standardized methionine challenge demonstrated altered vascular reactivity. In contrast, the cerebral autoregulation mechanism was shown to be unaffected by the same methionine load. To obtain additional insight into the compensatory range of the cerebral vasculature during a methionine challenge, we tested the neurovascular coupling mechanism that adjusts cerebral blood flow in accordance with cortical activity.
  
  
  METHODS
  Fifteen healthy young adults (age, 24.7+/-2.3 years; 7 men) were tested with a functional transcranial Doppler test before and 3, 8, and 24 hours after administration of placebo, 20 mg folic acid, 20 mg folic acid and 0.1 g/kg body weight L-methionine, or L-methionine alone. Evoked blood flow response was evaluated according to a control system approach. Plasma concentrations of homocysteine, resting blood flow velocities, and control system parameters of flow velocity change were compared for each time point using a multiple analysis of variance test.
  
  
  RESULTS
  Homocysteine levels increased significantly compared with baseline (before, 7.6+/-1.9 micromol/L; 3 hours, 22.2+/-6.0 micromol/L [P<0.0001]; 8 hours, 27.9+/-8.6 micromol/L [P<0.0001]; 24 hours, 12.6+/-7.8 micro mol/L [P=NS]). Resting flow velocities and control system parameters remained statistically nonsignificant.
  
  
  CONCLUSIONS
  Compared with the peripheral vasculature, the regulatory mechanisms controlling adequate cerebral blood flow appear to have a wider compensatory range. This is concluded from statistically nonsignificant results comparing the vascular reactivity in young adults undergoing a standardized methionine challenge. Our data confirm indirectly the reports of high concentrations of homocysteine needed to affect the cerebral vasculature in animal experiments.
authors.affiliation: Department of Neurology, Faculty of Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Rosengarten
authors.forename: S
authors.initials: S
authors.lastname: Osthaus
authors.forename: D
authors.initials: D
authors.lastname: Auch
authors.forename: M
authors.initials: M
authors.lastname: Kaps
mesh_terms: D000208:Acute Disease; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced; D008297:Male; D008715:Methionine; D010775:Photic Stimulation; D020769:Posterior Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013599:Systole; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D008715:Methionine