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 ω-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. (J Lab Clin Med 2000;135:419-25)
Abbreviations:
eNOS (endothelial nitric oxide), HDL (high-density lipoprotein), HPLC (high-performance liquid chromatography), iNOS (inducible nitric oxide), LDL (low-density lipoprotein), l-NHA (Nω-hydroxy-l-arginine), NO (nitric oxide), NOS (nitric oxide synthase)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607
- The pathogenesis of atherosclerosis: a perspective for the 1990s.Nature. 1993; 362: 801-809
- Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis.Circulation. 1991; 83: 391-401
- Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension.N Engl J Med. 1990; 323: 22-27
- Non-invasive assessment of cardiovascular disease in diabetes mellitus.Lancet. 1997; 350: SI14-SI19
- Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus.J Am Coll Cardiol. 1996; 27: 567-574
- Nitric oxide synthases: which, where, how and why?.J Clin Invest. 1998; 100: 2146-2152
- Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity.Circulation. 1992; 85: 1927-1938
- Atherosclerosis and the two faces of endothelial nitric oxide synthase.Circulation. 1998; 97: 108-112
- Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway.Circulation. 1995; 91: 1732-1738
- Increases of NO2/NO3-excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure.Clin Sci. 1992; 82: 631-634
- Measurement of serum levels of nitrate ions in men and women. Implications of endothelium-derived relaxing factor in blood pressure regulation and atherosclerosis.J Cardiovasc Pharmacol. 1992; 20: 214
- Long-term administration of L -arginine, L -NAME and the exogenous NO donor molsidomine modulates urinary nitrate and cGMP excretion in rats.Cardiovasc Res. 1994; 28: 494
- Supplementation of hypercholesterolaemic rabbits with L -arginine reduces the vascular release of superoxide anions and restores NO production.Atherosclerosis. 1995; 117: 273-284
- Dietary L -arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin.Circulation. 1997; 96: 1282-1290
- Urinary nitrate excretion is increased in cardiac transplanted patients with acute graft rejection.Clin Transplant. 1996; 10: 298-305
- N omega-hydroxy-L -arginine is an intermediate in the biosynthesis of nitric oxide from L -arginine.J Biol Chem. 1991; 266: 6259-6263
- Increased serum NG-hydroxy-L -arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity.Ann Rheum Dis. 1997; 56: 330-332
- State-of-the-art of high-performance liquid chromatographic analysis of amino acids in physiological samples.J Chromatogr B. 1996; 682: 3-22
- Endothelial cells metabolize NG-monomethyl-L -arginine to L -citrulline and subsequently to L -arginine.Biochem Biophys Res Commun. 1990; 167: 1037-1043
- Increase in serum NG-hydroxy-L -arginine in rats treated with bacterial lipopolysaccharide.Eur J Pharmacol. 1995; 275: R1-R3
- Oxidative denitrification of N omega-hydroxy-L -arginine by the superoxide radical anion.Biochem J. 1996; 317: 17-21
- Exogenous NG-hydroxy-L -arginine causes nitrite production in vascular smooth muscle cells in the absence of nitric oxide synthase activity.FEBS Lett. 1994; 341: 203-207
- Smoking impairs the activity of endothelial nitric oxide synthase in saphenous vein.Arterioscler Thromb Vasc Biol. 1996; 16: 546-552
- N omega-hydroxy-L -arginine: a novel arginine analog capable of causing vasorelaxation in bovine intrapulmonary artery.Biochem Biophys Res Commun. 1991; 176: 528-534
- Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults.N Engl J Med. 1996; 334: 150-154
- The endothelium in coronary artery disease.Cardiology. 1997; 88: 3-19
- Effect of chronic angiotensin-converting enzyme inhibition on endothelial function in patients with chronic heart failure.Am J Cardiol. 1995; 76: 13E-18E
- Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication.Lancet. 1995; 346: 467-471
- Modulation of endothelial function: strategy for long-term cardiovascular protection.J Hypertens Suppl. 1996; 14: S27-S32
- Endothelial dysfunction: does it matter? Is it reversible?.J Am Coll Cardiol. 1997; 30 (1997): 325-333
Article info
Publication history
Accepted:
January 19,
2000
Received:
January 10,
2000
Footnotes
☆Reprint requests: Christoph D. Garlichs, MD, Friedrich-Alexander-Universität Erlangen-Nürnberg, Medical Clinic II, c/o David-Morgenstern-Weg 14, 91056 Erlangen, Germany.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
