Electron paramagnetic resonance investigation on modulatory effect of 17beta-estradiol on membrane fluidity of erythrocytes in postmenopausal women.
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 17beta-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.
Tsuda
K
K
Division of Cardiology, Department of Medicine, Wakayama Medical University, Wakayama, Japan. tsudak@mail.wakayama-med.ac.jp
Kinoshita
Y
Y
Kimura
K
K
Nishio
I
I
Masuyama
Y
Y
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006973:Hypertension; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D017698:Postmenopause / Q000097:blood* / Q000502:physiology; D026423:S-Nitroso-N-Acetylpenicillamine
D020030:Nitric Oxide Donors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D004958:Estradiol; C018524:N,N-dimethylarginine; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D010396:Penicillamine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester