Electron Paramagnetic Resonance Investigation on Modulatory Effect of 17β-Estradiol on Membrane Fluidity of Erythrocytes in Postmenopausal Women

Abstract

Abstract-Many studies have shown that estrogen may exert cardioprotective effects and reduce the risk of hypertension and coronary events. On the other hand, it has been proposed that cell membrane abnormalities play a role in the pathophysiology of hypertension, although it is not clear whether estrogen would influence membrane function in essential hypertension. The present study was performed to investigate the effects of 17␤-estradiol (E 2 ) on membrane fluidity of erythrocytes in normotensive and hypertensive postmenopausal women. We determined the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance and spin-labeling method. In an in vitro study, E 2 significantly decreased the order parameter for 5-nitroxide stearate and the peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive postmenopausal women. The finding indicates that E 2 might increase the membrane fluidity of erythrocytes. The effect of E 2 was significantly potentiated by the NO donor, S-nitroso-N-acetylpenicillamine, and a cGMP analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by E 2 was attenuated in the presence of the NO synthase inhibitor, N G -nitro-L-arginine methyl ester, and asymmetric dimethyl-L-arginine. In hypertensive postmenopausal women, the membrane fluidity of erythrocytes was significantly lower than that in normotensive postmenopausal women. The effect of E 2 on membrane fluidity was significantly more pronounced in the erythrocytes of hypertensive postmenopausal women than in the erythrocytes of normotensive postmenopausal women. The results of the present study showed that E 2 significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO-and cGMP-dependent pathway. Furthermore, the greater action of E 2 in hypertension might be consistent with the hypothesis that E 2 could have a beneficial effect in regulating rheological behavior of erythrocytes and could have a crucial role in the improvement of the microcirculation in hypertension. here is a strong link between menopause and an increased incidence of cardiovascular diseases, and recent studies have demonstrated that estrogen replacement therapy reduced morbidity or mortality due to coronary heart diseases in postmenopausal women. [1][2][3][4] It has also been shown that estrogen supplementation induced a significant fall in blood pressure in postmenopausal women. 5 These findings propose the idea that estrogen may exert protective effects against arteriosclerosis and hypertension. However, fundamental mechanisms of cellular and molecular events by estrogen are still unclear.It has been proposed that cell membrane abnormalities are an etiological factor in hypertension, including functional abnormalities, such as transmembrane cation fluxes. 6 -8 An electron paramagnetic resonance (EPR) and spin-labeling method have been developed to elucidate the membrane fluid...

Oxidative Stress and Membrane Fluidity of Red Blood Cells in Hypertensive and Normotensive Men An Electron Spin Resonance Investigation

“…The RBC preparation and ESR measurement procedures have been described previously. [9][10][11][12][13] We evaluated the values of outer and inner hyperfine splitting (2T' ￨￨ and 2T' ⏊ in G, respectively) in the ESR spectra for the spin label agent (5-nitroxide stearate, Aldrich Co. Ltd., Milwaukee, Wisconsin, USA) and calculated the order parameter (S). [9][10][11][12][13] The greater the value of the order parameter (S) was, the lower the membrane fluidity of RBCs.…”

“…[9][10][11][12][13] We evaluated the values of outer and inner hyperfine splitting (2T' ￨￨ and 2T' ⏊ in G, respectively) in the ESR spectra for the spin label agent (5-nitroxide stearate, Aldrich Co. Ltd., Milwaukee, Wisconsin, USA) and calculated the order parameter (S). [9][10][11][12][13] The greater the value of the order parameter (S) was, the lower the membrane fluidity of RBCs. [9][10][11][12][13] Plasma 8-Iso-PG F2α levels were determined by using an enzyme immunoassay (Cayman Chemicals Co., Ann Arbor, Michigan, USA).…”

“…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 membrane fluidity of RBCs could cause a disturbance in the blood rheologic behavior and in the microcirculation, which might contribute to the pathophysiology of hypertension and other circulatory disorders.…”

“…[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 membrane fluidity of RBCs could cause a disturbance in the blood rheologic behavior and in the microcirculation, which might contribute to the pathophysiology of hypertension and other circulatory disorders. 8,9) In the present study, in order to assess the role of oxidative stress in the regulation of membrane function in hypertension, we investigated the relationships between plasma 8-Iso-PG F2α and membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men.…”

A New Hormone Therapy With Drospirenone and NO Production in Postmenopausal Women

“…2 In a study presented earlier, we showed that E2 increased membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and improved the rigidity of cell membranes in postmenopausal women via the NO-dependent mechanism. 3 Because abnormalities in membrane microviscosity could cause a disturbance in the rheological behavior of erythrocytes and the microcirculation, estrogen might be favorable for the prevention of circulatory disorders in postmenopausal women. In addition, we demonstrated that progesterone and NO might have a synergistic effect on the improvement of membrane microviscosity of erythrocytes.…”