Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation

Background It has been shown that progesterone may actively participate in the regulation of blood pressure and other cardiovascular regulations. However, the precise mechanism underlying its effects is unclear. Methods In the present study, we examined the effects of progesterone on membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method. Results In an in vitro study, progesterone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes. The finding indicates that progesterone might increase the membrane fluidity and improve the membrane microviscosity of erythrocytes. The effect of progesterone was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP) and a cyclic guanosine monophosphate (cGMP) analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by progesterone was attenuated in the presence of the NO synthase inhibitors, NG-nitro- -arginine-methyl-ester (L-NAME) and asymmetric dimethyl- -arginine (ADMA). Conclusions The results of the present study showed that progesterone increased the membrane fluidity of erythrocytes and ameliorated the rigidity of cell membranes, at least in part, by an NO-dependent mechanism. Furthermore, the data strongly suggest that progesterone might be involved in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation in humans.