Decreased plasma concentrations of L-hydroxyarginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors

Patients with metabolic syndrome represent a group with extensive cardiovas cular risk factors for the development of atherosclerosis, which may be pre ceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the prin cipal 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 compoun d N-omega-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequ isite to our study we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether bloo d drawn from peripheral veins reflects plasma concentrations of the whole v essel system, several blood samples from different regions were obtained fr om patients undergoing elective left and right heart catheterization. In th e latter group, no significant differences were noted among the plasma conc entrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specif ic 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 signi ficantly reduced in the plasma samples of patients with a metabolic syndrom e as compared with samples from healthy control subjects. The plasma concen trations of the NO precursor L-arginine and the end product of NO synthesis , L-citrulline, were unchanged. in conclusion, our results suggest that pla sma level 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 c oncentrations of L-NHA, either caused by a decreased endothelial NO synthas e activity or caused by an increased breakdown of L-NHA by pathways indepen dent of NO synthase, resulting in a reduced availability of L-NHA for NO sy nthesis.