Hormone replacement therapy improves membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation

BACKGROUND: Many studies have shown that hormone replacement therapy (HRT) might provide protection against the development of hypertension and arteriosclerosis in postmenopausal women. However, the precise mechanism underlying its benefits is unclear. This question was addressed in an electron spin resonance (EPR) study of membrane function of erythrocytes in postmenopausal women. The purpose of this study was to investigate the effects of HRT on membrane fluidity of erythrocytes in postmenopausal women by means of the EPR and spin-labeling method. METHODS: The healthy postmenopausal women were randomly divided into the HRT group (n = 14) receiving the conjugated estrogen with medroxyprogesterone for 3 months and the non-HRT control group (n = 14). We measured membrane fluidity of erythrocytes in postmenopausal women before and after the trial period. RESULTS: The HRT group showed a significant decrease in blood pressure (BP) after treatment (systolic BP 145.7 +/- 5.5 v 123.3 +/- 5.1 mm Hg, n = 14, mean +/- SEM, P <.05). The order parameter (S) for 5-nitroxide stearate in the EPR spectra of erythrocyte membranes decreased significantly in the HRT group (S: 0.718 +/- 0.002 v 0.695 +/- 0.002, n = 14, P <.01). The finding indicated that HRT increased the membrane fluidity of erythrocytes and improved the microviscosity of the cell membranes in postmenopausal women. CONCLUSIONS: These results are consistent with the hypothesis that HRT might have a beneficial effect on the membrane rheologic behavior of erythrocytes and the microcirculation in postmenopausal women.     

Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation

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.     

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.     

Leptin and membrane fluidity of erythrocytes in essential hypertension. An electron paramagnetic resonance investigation

There has been an indication that leptin, the product of the human obesity gene, actively participates not only in metabolic regulation but also in the control of blood pressure. Recently, it has been proposed that abnormalities in the physical property of cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. We have shown previously that leptin significantly increased the membrane fluidity and improved the microviscosity of erythrocytes in humans through the nitric oxide-dependent mechanism. In the present study, we examined the effects of leptin on membrane fluidity of erythrocytes in subjects with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The values of the order parameter (S) and the peak height ratio (ho/h-1) obtained from the EPR spectra of erythrocytes were significantly greater in patients with essential hypertension (HT) than in age-matched normotensive subjects (NT) (S: HT 0.719 +/- 0.002, n = 16, NT 0.713 +/- 0.001, n = 29, P < .05; ho/h-1: HT 5.17 +/- 0.02, n = 16, NT 5.05 +/- 0.02, n = 29, P < .05). The finding indicated that the erythrocyte membrane fluidity was lower in patients with HT than in NT. Leptin decreased S and ho/h-1 in a dose-dependent manner in both NTs and HTs. The effect of leptin on the membrane fluidity was significantly more pronounced in HTs than in NTs (percent change in S: leptin 10(-8) g/mL, HT -3.4% +/- 0.2%, n = 16, NT -2.3% +/- 0.1%, n = 29, P < .05; leptin 10(-7) g/mL, HT -4.3% +/- 0.3%, n = 16, NT -3.3% +/- 0.1%, n = 29, P < .05). The results of the present study showed that leptin might have a crucial role in the regulation of the rheologic behavior of erythrocytes and the microcirculation in hypertension.     

Association of resistin with impaired membrane fluidity of red blood cells in hypertensive and normotensive men: an electron paramagnetic resonance study

Abnormalities in physical properties of the cell membranes may strongly be linked to hypertension. Recent evidence indicates that resistin may actively participate in the pathophysiology of insulin resistance, diabetes mellitus, hypertension and other circulatory disorders. The present study was undertaken to investigate the possible relationships among plasma resistin, oxidative stress and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron paramagnetic resonance (EPR) and spin-labeling method. The order parameter (S) for the spin-label agents (5-nitroxide stearate) in EPR spectra of red blood cell (RBC) membranes was significantly higher in hypertensive men than in normotensive men, indicating that membrane fluidity was decreased in hypertension. Plasma resistin levels were correlated with systolic blood pressure and 8-iso-prostaglandin F2α levels (an index of oxidative stress). Furthermore, the order parameter (S) of RBCs significantly correlated with plasma resistin and plasma 8-isoPG F2α, suggesting that reduced membrane fluidity of RBCs might be associated with hyperresistinemia and increased oxidative stress. Multivariate regression analysis showed that, after adjustment for confounding factors, plasma resistin might be an independent determinant of membrane fluidity of RBCs. The EPR study suggests that resistin might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory dysfunction in hypertension, at least in part, via an oxidative stress-dependent mechanism.     

Role of insulin in the regulation of membrane fluidity of erythrocytes in essential hypertension: an electron paramagnetic resonance investigation

In the present study, to determine a possible role of insulin in the regulation of membrane functions, we have examined the effects of insulin on the membrane fluidity of erythrocytes in patients with essential hypertension and normotensive subjects. Membrane fluidity of erythrocytes obtained from hypertensive and normotensive subjects were evaluated by means of an electron paramagnetic resonance (EPR) and a spin-labeling method. In an in vitro study, insulin increased the order parameter (S for 5-nitroxide stearate) and the peak height ratio (ho/h-1 for 16 nitroxide stearate) in the EPR spectra of erythrocyte membranes, which indicated that insulin decreased the membrane fluidity of erythrocytes. The effects of insulin on the membrane fluidity were potentiated in the presence of extracellular Ca²⁺, and in contrast, were antagonized by the Ca²⁺ channel blocker diltiazem. Furthermore, the effects of insulin alone and in combination with Ca²⁺ on the membrane fluidity were reduced in the erythrocytes from hypertensive subjects compared with the erythrocytes from normotensive controls. The high concentrations of glucose alone produced no significant effects on the membrane fluidity of erythrocytes. These results demonstrated that insulin might actively participate in the regulation of membrane fluidity of erythrocytes, which might be mediated by the intracellular Ca²⁺ kinetics.     

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, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-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.     

Estriol improves membrane fluidity of erythrocytes by the nitric oxide-dependent mechanism: an electron paramagnetic resonance study.

The present in vitro study was performed to investigate the effects of estriol (E3) on membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labeling method. E3 was shown to significantly decrease 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. This finding indicated that E3 might increase the membrane fluidity of erythrocytes. The effect of E3 was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine 3',5'-monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change in the membrane fluidity induced by E3 was antagonized by the NO synthase inhibitor, L-NG-nitroarginine-methyl-ester (L-NAME), and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that E3 significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the data might be consistent with the hypothesis that E3 could have a beneficial effect on the rheological behavior of erythrocytes and may play a crucial role in the regulation of microcirculation.     

Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women

Selective estrogen receptor modulators, like tamoxifen and related compounds, have mixed estrogen agonistic/antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with conjugated estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol (P<0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) (P<0.05). In contrast, estrogen, but not droloxifene, increased high density lipoprotein (18.5%, P<0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with estrogen (P=0.004) but produced no estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, P<0.05 for both). Droloxifene has estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit.     

Electron paramagnetic resonance investigation on modulatory effect of benidipine on membrane fluidity of erythrocytes in essential hypertension

It has been shown that benidipine, a long-lasting calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate whether orally administered benidipine might influence the membrane function in patients with essential hypertension. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. In the preliminary study using erythrocytes obtained from healthy volunteers, benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS in the EPR spectra in vitro. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. In addition, it was demonstrated that the effect of benidipine on membrane fluidity of erythrocytes was significantly potentiated by the NO-substrate, L-arginine. In the separate series of the study, we observed that orally administered benidipine for 4 weeks significantly increased the membrane fluidity of erythrocytes with a concomitant increase in plasma NO metabolite levels in hypertensive subjects. The results of the present study demonstrated that benidipine might increase the membrane fluidity and improve the microviscosity of erythrocytes both in vitro and in vivo, to some extent, by the NO-dependent mechanism. Furthermore, it is strongly suggested that orally administered benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in hypertensive subjects.     

Effect of HMR 3339, a novel selective estrogen receptor modulator, on C-reactive protein levels in healthy postmenopausal women

We investigated the 12-week effects of 3 doses of HMR 3339, a novel selective estrogen receptor modulator, in comparison with raloxifene and placebo, on plasma concentrations of C-reactive protein in 96 healthy postmenopausal women. A dose-dependent reduction in C-reactive protein was observed, the largest reduction with HMR 3339 50 mg.     

Update on bazedoxifene: A novel selective estrogen receptor modulator

In the elderly population, osteoporosis is a significant clinical problem leading to disability and even death. Many patients remain untreated, despite effective therapies, because of patients’ unwillingness to take current therapies or inability to tolerate the therapies. For this reason, ongoing research continues to search for more effective and tolerable osteoporosis agents. Bazedoxifene is a selective estrogen receptor modulator (SERM) currently in development for osteoporosis prevention and treatment. A new drug application (NDA) for postmenopausal osteoporosis prevention was recently submitted to the FDA. Preclinical and clinical studies with bazedoxifene demonstrate more tissue selectivity than other SERMs. In particular, bazedoxifene has minimal if any agonist activity in the uterus and is able to antagonize effects of estrogen on the uterus. Animal studies and early clinical studies suggest effects in the bone similar to other SERMs with prevention of postmenopausal bone loss. Until more data on efficacy and safety are published, however, its role in osteoporosis is unknown.     

选择性雌激素受体调节剂对绝经后乳腺癌患者子宫内膜的影响

目的 探讨应用选择性雌激素受体调节剂(SERM)的绝经后乳腺癌患者子宫内膜病变相关因素及筛查方法.方法 分析上海市长宁区妇幼保健院2013年1月至2020年6月间84例口服SERM的绝经后乳腺癌患者因经阴道超声(TVS)发现子宫内膜增厚行宫腔镜下子宫内膜活检术患者的临床资料.结果 宫腔镜术前有13例(15.5％)患者有...     

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.     

Effects of ouabain on membrane fluidity of erythrocytes in essential hypertension. An electron spin resonance study.

In the present study, we have examined the effects of ouabain on membrane fluidity of erythrocytes by use of an electron spin resonance (ESR) and spin-labeling method, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects, and the ESR spectra for 5-nitroxy stearate incorporated into erythrocyte membranes were studied. The values of outer hyperfine splitting and order parameter (S) of the ESR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain loading to erythrocytes decreased the membrane fluidity (S value was increased). The alternative degree was significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.     

Effects of raloxifene, one of the selective estrogen receptor modulators, on pituitary-ovary axis and prolactin in postmenopausal women

To investigate the clinical effects of raloxifene, one of the selective estrogen receptor modulators (SERMs), on the pituitary-ovary axis and prolactin, a prospective, randomized, double-blinded study on 59 healthy postmenopausal women was performed. Forty-eight women received raloxifene 60 mg daily. The other 11 received combined conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 5 mg daily (CCEP) as active controls. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin were measured at baseline and 1 yr after treatment. The mean levels of FSH and LH were significantly decreased in the raloxifene group (FSH: −10.7%; p<0.01, LH: −10.3%; p<0.05) and CCEP group (FSH: −53.7%, p<0.001; LH: −46.8%, p<0.001). The prolactin level decreased in the raloxifene group but not in the CCEP group (−17.0%; p<0.001 vs + 13.3%, p=no significance; NS). Consequently, long-term administration of raloxifene up to 1 yr decreases serum prolactin level significantly and may be a therapeutic alternative for postmenopausal osteoporotic women with hyperprolactinemia.     

Effects induced by olive oil-rich diet on erythrocytes membrane lipids and sodium-potassium transports in postmenopausal hypertensive women.

Since we have observed that monounsaturated fatty acids (MUFA) enriched diet modifies red cell membrane lipids and cation transport systems in normotensive subjects, we similarly evaluated a group of hypertensive patients undergoing an analogous dietary modification. In a group of 18 moderately hypertensive women, the diet was supplemented for two months with olive oil (about 45 g/day), which replaced an equal amount of seasoning fats. Before and after this period, red cell fatty acid composition was evaluated by gas-chromatography in order to verify diet compliance: a significant increase in oleic acid was observed, while the content of saturated and polyunsaturated fatty acids remained unchanged. After olive oil, maximal rates of Na-K pump (5580 +/- 329 vs 6995 +/- 390, p less than 0.001) and Na-K cotransport (Na-COT 544 +/- 52 vs 877 +/- 46, p less than 0.001: K-COT 790 +/- 76 vs 1176 +/- 66, p less than 0.001), cell Na content (9.58 +/- 0.4 vs 10.61 +/- 0.6, p less than 0.03) and passive permeability for Na (936 +/- 74 vs 1836 +/- 102, p less than 0.001) rose significantly. Although the reduction in maximal rate of the Li-Na CT after olive oil was not significant, it was the only cation transport parameter being correlated with the variations of membrane lipids, namely negatively with UFA (r = -0.528, p less than 0.05) and positively with SFA (r = 0.482, p less than 0.005). The change in maximal rate of Li-Na CT was also correlated with the variation of systolic and diastolic BP (r = 0.50, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of estrogen receptor modulator tamoxifen on blood pressure,plasma renin activity,and renal sodium excretion

BACKGROUND: Adjuvant treatment with the estrogen receptor modulator tamoxifen is a well established long-term therapy in breast cancer. This study investigated the effect of tamoxifen on blood pressure (BP) and on factors by which it might be influenced. METHODS: Normotensive postmenopausal women on > 12 months adjuvant tamoxifen therapy were randomized to withdraw or continue tamoxifen for 6 weeks and then to crossover to the alternative regimen for a second 6-week period. Measurements of clinic and ambulatory BP, plasma renin activity (PRA), and fractional sodium excretion (FE(Na)) were performed at baseline and at the end of each study period. RESULTS: Twenty-three women completed the study (mean age 60.6 +/- 8.3 years). There was no effect of tamoxifen on clinic BP (mean difference between withdrawal and continuation for systolic BP, 0.4 +/- 8.4 mm Hg, 95% confidence interval [CI] -4.0 to 3.2, and diastolic 0.6 +/- 4.7, 95%CI -1.4 to 2.7) or 24-hour ambulatory BP (systolic 0.7 +/- 7.4 mmHg, 95%CI -2.6 to 3.9; diastolic BP, 1.9 +/- 5.5, 95% CI -0.5 to 4.2). Furthermore, no effect of tamoxifen on PRA (mean difference between withdrawal and continuation 0.03 +/- 0.5 ng/mL/h, 95% CI -0.3 to 0.2) or FENa (0.05 +/- 0.5, 95% CI -0.2 to 0.2) was detected. CONCLUSIONS: Tamoxifen seems to have no effect on BP, PRA, or FE(Na) in normotensive postmenopausal women.