In the present study, to determine a possible role of nitric oxide (NO) in the regulation of membrane functions, we examined the relationship between plasma NO level and membrane fluidity of erythrocytes in postmenopausal women. We evaluated the membrane fluidity of erythrocytes obtained from hypertensive and normotensive postmenopausal women by means of an electron paramagnetic resonance (EPR) and spin labeling method. The EPR study revealed that the order parameter (S) for 5-nitroxide stearate in erythrocyte membranes was significantly greater in hypertensive postmenopausal women than in normotensive postmenopausal women. The finding indicated that the membrane fluidity of erythrocytes was decreased in hypertensive postmenopausal women compared with normotensive postmenopausal women. The plasma level of the NO metabolites (nitrite and nitrate) while fasting was significantly lower in hypertensive postmenopausal women than in normotensive postmenopausal women. In addition, the order parameter (S) in the EPR spectra of erythrocyte membranes was inversely correlated with the plasma NO metabolite level, which indicated that the lower membrane fluidity of erythrocytes was associated with the lower plasma NO level in postmenopausal women. These results are consistent with the hypothesis that NO may have a crucial role in the regulation of membrane fluidity of erythrocytes in postmenopausal women.

1. It has been recognized that hormone replacement therapy (HRT) may have a beneficial effect on protection against cardiovascular diseases. Oestrone is the major component of conjugated equiline oestrogens, which are commonly used in HRT. The present study was performed in order to investigate the effects of oestrone on the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labelling method. 2. In an in vitro study, oestrone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-nitroxide stearate (16-NS) obtained from EPR spectra of erythrocyte membranes. This finding indicated that oestrone may increase the membrane fluidity and improve the membrane microviscosity of erythrocytes. 3. The effect of oestrone was significantly potentiated by the nitric oxide (NO) donor s-nitroso-N-acetylpenicillamine and the cGMP analogue 8-bromo-cGMP. 4. In contrast, the change in membrane fluidity induced by oestrone was antagonized by the NO synthase inhibitors NG-nitro-l-arginine methyl ester and asymmetric dimethyl-l-arginine. 5. The results of the present study show that oestrone significantly increases membrane fluidity and improves the rigidity of cell membranes, which is partially mediated by a NO- and cGMP-dependent pathway. Furthermore, the data may be consistent with the hypothesis that oestrone could have a beneficial effect on the rheological behaviour of erythrocytes and have a crucial role in the regulation of the microcirculation.