Abstract 1196: Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics And Subclinical Vascular Disease: A Population-based Study
Background: Asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (NMMA), endogenous nitric oxide-synthase inhibitors (End-NOSI), have been associated with cardiovascular risk factors (CVRF) and atherosclerosis. In addition, acute administration of NOSI cause hypertension through hemodynamic effects, but whether circulating End-NOSI are associated with these abnormalities is unknown.
Methods: We studied 922 adults in a population-based study (PREVENCION study). We examined the correlation between End-NOSI/L-arginine and CVRF, as well as the relationship between these biomarkers and arterial hemodynamics, carotid-femoral pulse wave velocity (cf-PWV) and carotid intima-media thickness (c-IMT). We used general linear modeling for statistical analyses. Estimates (β) are standardized.
Results: In multivariate analyses, LDL-cholesterol and C-reactive protein (CRP) were independent predictors of ADMA, whereas LDL-cholesterol and gender independently predicted NMMA. Age, gender, HDL-cholesterol and CRP were independent predictors of L-arginine. ADMA (β=0.09;p=0.008) and NMMA (β=0.11; p=0.001), but not L-arginine, were strong predictors of c-IMT, even after adjustment for CVRF, CRP and renal function. In contrast, ADMA and NMMA were not predictors of cf-PWV, blood pressure or hemodynamic abnormalities. Higher L-arginine independently predicted higher central (aortic) pulse pressure (β=0.09; p=0.002), incident wave amplitude (β=0.11; p<0.001) and late systolic augmented pressure from wave reflections (β=0.07; p=0.003), but not systemic vascular resistance or cardiac output.
Conclusions: ADMA and NMMA are differentially associated with CVRF, but both End-NOSI are independently predictors of carotid atherosclerosis. In contrast, they are not associated with large artery stiffness, hypertension or hemodynamic abnormalities. Our findings are consistent with a role for End-NOSI in atherosclerosis, but not in large artery stiffnening, hypertension or long-term hemodynamic regulation. L-arginine is independently associated with abnormal pulsatile hemodynamics, which may reflect abnormal L-arginine transport, leading to decreased intracellular bioavailability for NO synthesis.