SummaryRecent evidence indicates that oxidative stress might actively participate in the pathophysiology of hypertension, atherosclerosis, and other cardiovascular diseases. The purpose of the present study was to assess the possible link between oxidative stress and membrane fluidity in hypertensive and normotensive men. We measured the membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was decreased in hypertensive men compared with normotensive men. The levels of plasma 8-Iso-prostaglandin F2α (8-Iso-PG F2α : an index of oxidative stress) were significantly higher in hypertensive men than in normotensive men. In contrast, plasma nitric oxide (NO)-metabolite levels were significantly lower in hypertensive men than in normotensive men. In the overall analysis of hypertensive and normotensive men, plasma 8-Iso-PG F2α levels were inversely correlated with plasma NO-metabolites. Furthermore, the reduced membrane fluidity of RBCs was associated with increased plasma 8-Iso-PG F2α and decreased plasma NO-metabolite levels. In a multivariate regression analysis, plasma 8-Iso-PG F2α was found to be an independent determinant of membrane fluidity of RBCs participate in the pathophysiology of hypertension and atherosclerosis, and might be associated with increased risk of cardiovascular diseases, vascular dysfunction, and the metabolic syndrome.1-3) Recent studies have shown that plasma 8-Iso-prostaglandin F2α (8-Iso-PG F2α ) may be a reliable index of oxidative stress in humans. [4][5][6][7] It was demonstrated that the plasma concentration of 8-Iso-PG F2α was significantly increased in subjects with essential hypertension compared with normotensive subjects. 4,5) It has also been shown that plasma 8-Iso-PG F2α levels were elevated in patients with coronary artery disease, particularly in those with hypertension. 6,7) However, cellular mechanisms of oxidative stress in the pathophysiology of hypertension are not fully understood.Abnormalities in the physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular disease conditions. 8,9) An electron spin resonance (ESR) and spinlabeling method has been developed to evaluate the membrane fluidity (a reciprocal value of membrane microviscosity) and the perturbations of membrane function by external agents. 8,9) Using the ESR method, we have been performing a series of experiments regarding the membrane fluidity in subjects with essential hypertension. [9][10][11][12][13] The results suggest that the membrane fluidity of red blood cells (RBCs) was significantly lower in hypertensive subjects than in normotensive subjects, indicating that the cell membranes were stiffer and less fluid in essential hypertension. [9][10][11][12][13] Because the deformability of RBCs may be highly dependent on the membrane fluidity, 8) the reduction in...