An Association Between Plasma Asymmetric Dimethylarginine and Membrane Fluidity of Erythrocytes in Hypertensive and Normotensive Men: An Electron Paramagnetic Resonance Investigation

Background Evidence indicates that increased levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, are associated with increased risk of vascular dysfunction. The present study was performed to assess the possible relationship between plasma ADMA levels and membrane fluidity in hypertensive and normotensive men. Methods Membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes in hypertensive (n = 38) and normotensive (n = 35) men were measured using an electron paramagnetic resonance (EPR) and spin-labeling method. Results The order parameter (S) for the spin-label agent (5-nitroxide stearate) in the EPR spectra of erythrocyte membranes was significantly higher in hypertensive men than in normotensive men (mean ± SEM: hypertensive subjects, 0.725 ± 0.001,n = 38; normotensive subjects, 0.713 ± 0.001, n = 35, P< .001), indicating that membrane fluidity of erythrocytes was decreased in hypertensive men compared with normotensive men. Plasma NO metabolite (nitrite and nitrate) concentration was lower in hypertensive than in normotensive men. In contrast, plasma ADMA levels were higher in hypertensive than in normotensive men. In the overall analysis of hypertensive and normotensive men, the order parameter (S) of erythrocytes was inversely correlated with plasma NO metabolites (r = −0.36, n = 73, P< .01) and positively correlated with plasma ADMA levels (r = 0.44, n = 73, P< .001), indicating that the reduced membrane fluidity of erythrocytes was associated with decreased NO and increased ADMA levels in plasma. When correlation analysis was performed separately for hypertensive and normotensive men, there was a positive correlation between plasma ADMA levels and the order parameter (S) of erythrocytes in both groups. Conclusions The results of the present study showed that the plasma ADMA levels were elevated in hypertensive men and associated with lower membrane fluidity of erythrocytes, suggesting that ADMA might have a close correlation with the rheologic behavior of erythrocytes and the microcirculation in hypertension.