title: Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors.
abstract: Patients with metabolic syndrome represent a group with extensive cardiovascular risk factors for the development of atherosclerosis, which may be preceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the principal mediator of endothelium-dependent vasodilation. In the present study we assessed NO synthesis in vivo by measuring the NO-related amino acids L-arginine and L-citrulline and in particular the stable intermediate compound N(omega)-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequisite to our study, we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether blood drawn from peripheral veins reflects plasma concentrations of the whole vessel system, several blood samples from different regions were obtained from patients undergoing elective left and right heart catheterization. In the latter group, no significant differences were noted among the plasma concentrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specific amino acid between males and females or age groups. The main finding of the study is that the intermediate product of NO synthesis, L-NHA, is significantly reduced in the plasma samples of patients with a metabolic syndrome as compared with samples from healthy control subjects. The plasma concentrations of the NO precursor L-arginine and the end product of NO synthesis, L-citrulline, were unchanged. In conclusion, our results suggest that plasma levels of L-NHA are independent of age and gender and are not different at various locations within the vascular system. In a group of patients at high risk for the development of atherosclerosis, we found reduced plasma concentrations of L-NHA, either caused by a decreased endothelial NO synthase activity or caused by an increased breakdown of L-NHA by pathways independent of NO synthase, resulting in a reduced availability of L-NHA for NO synthesis.
authors.affiliation: Medical Clinic II, Friedrich-Alexander-University Erlangen-Nürnberg, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Garlichs
authors.forename: J
authors.initials: J
authors.lastname: Beyer
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Schmeisser
authors.forename: K
authors.initials: K
authors.lastname: Plötze
authors.forename: A
authors.initials: A
authors.lastname: Mügge
authors.forename: S
authors.initials: S
authors.lastname: Schellong
authors.forename: W G
authors.initials: WG
authors.lastname: Daniel
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000097:blood; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood; D006973:Hypertension / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009765:Obesity / Q000097:blood; D012307:Risk Factors; D013577:Syndrome
chemical_list: D015415:Biomarkers; D002956:Citrulline; D009569:Nitric Oxide; C068309:N(omega)-hydroxyarginine; D001120:Arginine