Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavorable NOS substrate-to-inhibitor ratio - the Hoorn Study

Leonard P. van Der Zwan , Peter G Scheffer , Jacqueline M Dekker , Coen D.A. Stehouwer , Robert Heine , Tom Teerlink (1)

1 Department of Clinical Chemistry

Inflammation is associated with a reduced availability of nitric oxide (NO) in the vasculature. We investigated the possible involvement of altered levels of substrate (arginine) and inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase (NOS). Plasma concentrations of arginine and ADMA, the inflammatory markers C‑reactive protein (CRP) and myeloperoxidase (MPO), and oxidized LDL (oxLDL) were measured in 369 male and 377 female participants (aged 50 to 87 years) of a population-based cohort study. The arginine/ADMA ratio decreased significantly across increasing tertiles of CRP and MPO. These negative associations remained significant in a linear regression model with both MPO (P=0.002) and CRP (P<0.001) as independent variables and adjusted for age, sex and cardiovascular risk factors. In a fully adjusted regression model, MPO was positively associated with ADMA (5.4 [95% CI 1.3 to 9.4] nmol/L change of ADMA per SD increase of MPO; P=0.010), whereas CRP was not (P=0.36). Conversely, in a fully adjusted model, CRP was negatively associated with arginine (-2.8 [95% CI -4.0 to ‑1.6] µmol/L arginine per SD of CRP; P<0.001), without a significant contribution of MPO (P=0.23). The relationship between MPO and ADMA became stronger with increasing levels of oxLDL (1.8, 5.2, and 8.7 nmol/L ADMA per SD of MPO for increasing tertiles of oxLDL), consistent with the ability of MPO to amplify oxidative stress. In contrast, the relationship between CRP and arginine was not modified by levels of oxLDL. In conclusion, an unfavorable NOS substrate/inhibitor ratio may contribute to the reduced NO bioavailability associated with inflammation.

Mots clés: Medicine

Domaines: Médecine humaine et pathologie

Leonard P. van Der Zwan, Peter G Scheffer, Jacqueline M Dekker, Coen D.A. Stehouwer, Robert Heine, et al.. Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavorable NOS substrate-to-inhibitor ratio - the Hoorn Study. Clinical Science, 2011, 121 (2), pp.71-78. ⟨10.1042/CS20100595⟩. ⟨hal-00685071⟩