Asymmetric dimethylarginine (ADMA) and L-
homoarginine (hArg) are
L-arginine (Arg) metabolites derived from different pathways.
Protein arginine N-methyltransferase (PRMT) and subsequent proteolysis of
proteins containing methylarginine residues release ADMA.
Arginine:glycine amidinotransferase (AGAT) converts Arg to hArg and
guanidinoacetate (GAA). While high concentrations of ADMA and low concentrations of hArg in the blood have been established as cardiovascular risk markers, the cardiovascular relevance of GAA is still unexplored. Arg and hArg are substrates and ADMA is an inhibitor of
nitric oxide (
NO) synthase (NOS). The cardiovascular effects of ADMA and hArg have been related to NO, a potent endogenous
vasodilator. ADMA and hArg are considered to exert additional, not yet explored, presumably NO-unrelated effects and to act antagonistically in the renal and cardiovascular systems. Although the physiological role of Arg, ADMA, hArg and NO for endothelial function in small- and medium-sized arteries has been intensively studied in the past, the clinical relevance of aortic wall remodeling still remains unclear. Here, we evaluated potential relation between aortic distensibility (AD) or aortic intima-media thickness (aIMT) and circulating ADMA, hArg, GAA, and the NO metabolites
nitrite and
nitrate in the plasma of 78 patients (24 females, 54 males; aged 59 ± 14 years) with recent
ischemic stroke or
transient ischemic attack (TIA). All biochemical parameters were determined by stable-
isotope dilution gas chromatography-mass spectrometry. AD and aIMT were measured by transesophageal echocardiography. Arg, hArg, ADMA and GAA median plasma concentrations (µM) were determined to be 61, 1.43, 0.50 and 2.16, respectively. hArg, ADMA and GAA correlated closely with Arg.
Nitrite,
nitrate and
creatinine median plasma concentrations (µM) were 2.49, 48.7, and 84.1, respectively. Neither AD (2.61 vs. 1.85 10-6 × cm2 × dyn-1, P = 0.064) nor aIMT (1.25 vs. 1.13 mm, P = 0.596) differed between females and males. The hArg/ADMA molar ratio (r = -0.351, P = 0.009),
nitrate (r = 0.364, P = 0.007) and
nitrite (r = 0.329, P = 0.015) correlated with aIMT but not with AD. Arg, hArg, ADMA and GAA correlated with aIMT but not with AD. The results demonstrate a strong relation between the Arg/NO pathway and aortic
atherosclerosis but not with AD suggesting different mechanisms underlying the two aspects of aortic wall remodeling.