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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1306.)
© 2001 American Heart Association, Inc.

Vascular Biology

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

Kazushi Tsuda; Yukiko Kinoshita; Keizo Kimura; Ichiro Nishio; Yoshiaki Masuyama

From the Division of Cardiology (K.T., Y.K., K.K., I.N.), Department of Medicine, Wakayama Medical University, Wakayama, Japan, and Tokyo Rosai Hospital (Y.M.), Tokyo, Japan.

Correspondence to Kazushi Tsuda, MD, Division of Cardiology, Department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama 641-8509, Japan. E-mail tsudak{at}mail.wakayama-med.ac.jp

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 17ß-estradiol (E₂) 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, E₂ 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 E₂ might increase the membrane fluidity of erythrocytes. The effect of E₂ 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 E₂ 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 E₂ 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 E₂ 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 E₂ in hypertension might be consistent with the hypothesis that E₂ 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.

Key Words: 17ß-estradiol • nitric oxide • membrane fluidity • erythrocytes • postmenoapusal women

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