Modulatory Effects of Vascular Humoral Factors on Membrane Function in Metabolic Syndrome

研究表明，细胞膜物理性质的异常可能是与高血压、中风和其他心血管疾病密切相关的缺陷的基础。在本研究中，我们用电子自旋共振(ESR)方法检测了高血压合并代谢紊乱患者红细胞膜流动性(膜微粘度的倒数)。我们发现高血压患者红细胞膜流动性明显低于正常血压患者。结果表明，血浆一氧化氮(NO)代谢产物水平越低，红细胞膜流动性越低。血浆不对称二甲基精氨酸(ADMA)水平越高，红细胞膜流动性越低。高血压组血浆同型半胱氨酸浓度明显高于正常血压组。红细胞膜流动性降低与血浆同型半胱氨酸水平升高有关。在体外研究中，选择性雌激素受体调节剂(SERM)他莫昔芬可显著恢复老年女性红细胞膜流动性，这部分是通过NO依赖机制实现的。我们认为红细胞膜流动性降低可能导致血液流变性和微循环的紊乱，膜功能的改善至少部分有助于预防高血压和代谢综合征患者的循环障碍。

It has been shown that abnormalities in physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. In the present study, we examined the membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes in hypertensive subjects with metabolic disorders by using an electron spin resonance (ESR) method. We demonstrated that membrane fluidity of erythrocytes was significantly lower in hypertensive subjects than in normotensive subjects. It was shown that the lower was the plasma nitric oxide (NO) metabolite level, the lower was the membrane fluidity of erythrocytes. In contrast, the higher was the plasma asymmetric dimethylarginine (ADMA) level, the lower was the membrane fluidity of erythrocytes. Plasma homocysteine concentration was significantly increased in hypertensive subjects compared with normotensive subjects. The reduced membrane fluidity of erythrocytes was associated with higher plasma homocysteine levels. In an in vitro study, the selective estrogen receptor modulator (SERM), tamoxifen, significantly restored membrane fluidity of erythrocytes in elderly women, which was partially mediated by the NO-dependent mechanism. We propose that reduced membrane fluidity of erythrocytes might cause a disturbance in the blood rheologic behavior and the microcirculation, and that improvement of membrane function could contribute, at least in part, to the prevention against circulatory disorders in subjects with hypertension and the metabolic syndrome.