l-Arginine is related to endothelium-dependent vasodilation in resistance and conduit arteries in divergent ways—The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

Abstract

Background Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the conversion of l-arginine to the endothelium-derived vasodilator nitric oxide. We evaluated if circulating levels of l-arginine and ADMA, and the ratio thereof, were related to endothelium-dependent vasodilation in both resistance and conductance arteries in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study.Methods and results In this population-based study, vascular function of 1016 subjects aged 70 was evaluated by the invasive forearm technique with intra-brachial infusion of acetylcholine (EDV), by measurement of flow-mediated dilation (FMD) of the brachial artery, and by change in reflectance index (RI) by pulse wave analysis. After adjustment for resting forearm blood flow, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was positively related to EDV (P=0.005). This association was mainly driven by l-arginine, because if both l-arginine and ADMA were entered as predictor variables in a single regression model, l-arginine was positively associated with EDV (P=0.001), whereas the negative association between ADMA and EDV was not significant. In contrast, after adjustment for baseline brachial diameter, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was negatively related to FMD (P=0.004). Again, this association was mainly driven by l-arginine (P=0.002), whereas ADMA was not significantly related to FMD. The change in RI was not related to l-arginine, ADMA or their ratio.Conclusions In elderly subjects the l-arginine/ADMA ratio and l-arginine, but not ADMA, are positively related to endothelium-dependent vasodilation in resistance arteries, but negatively in a conduit artery.