Abstract 1148: Plasma Asymmetrical-Dimethyl-Arginine (ADMA) As A Regulator Of Vascular Redox And Nitric Oxide Bioavailability In Human Vessels
Background: The role of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), has been evaluated in-vitro and in animal models, but its effect in human vasculature is unclear. We examined the impact of plasma ADMA on endothelial NO bioavailability and superoxide radical (O2-) production in patients with advanced atherosclerosis.
Methods: Paired samples of saphenous veins (SV) and internal mammary arteries (IMA) were collected from 160 patients (65.2±0.6 yrs old) undergoing coronary bypass surgery. The vasomotor responses of SV segments to acetylcholine (Ach) were evaluated ex-vivo. Vascular O2- (in the presence or absence of eNOS inhibitor LNAME) was measured in paired SV and IMA, by lucigenin-enhanced chemiluminescence.
Results: High plasma ADMA levels were associated with decreased vasorelaxations of SV to Ach (Fig. a⇓). Similarly, ADMA was associated with higher O2- production in both SV and IMA (Fig b⇓), while there was a rather weak association between plasma ADMA and the LNAME-inhibitable O2- production in IMA (r=−0.259, p=0.008) but not in SV (r=−0.173, p=0.074). In multivariate linear regression, plasma ADMA was an independent predictor of vascular O2- (β(SE):3.39(0.416), p=0.0001), along with diabetes mellitus (p=0.042), dyslipidemia (p=0.018) and the angiographic extent of coronary atherosclerosis (p=0.048).
Conclusions: This is the first study demonstrating that ADMA has a direct impact on vascular NO bioavailability and O2- production in human vessels, in patients with coronary artery disease. However, further studies are required to elucidate the exact role of ADMA on eNOS coupling in human vessels.