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Abnormalities in Membrane Function and Ca-Metabolism in Hypertension, and Their Contribution to the Pathophysiology of the Metabolic Syndrome

高血压的膜功能和钙代谢异常及其对代谢综合征病理生理学的贡献

基本信息

批准号：
18590658
负责人：
TSUDA Kazushi
金额：
$ 2.44万
依托单位：
Kansai College of Oriental Medicine (2007)Wakayama Medical University (2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

In order to assess the membrane abnormalities in the metabolic syndrome, we investigated the vasoactive substances on the membrane fluidity in subjects with the metabolic syndrome. Membrane fluidity is a physicochemical feature of biomembranes and is an important factor modulating microcirculation. Using the electron paramagnetic resonance and spin-labeling method, we examine the alterations in membrane fluidity of erythrocytes in hypertensive subjects with obesity and diabetes mellitus. We demonstrated that the higher plasma insulin level, the lower the membrane fluidity of erythrocytes. This might indicate that hyperinsulinemia is involved in the regulation of membrane fluidity of erythrocytes. The decreased membrane fluidity of erythrocytes might cause a disturbance in the blood rheologic behavior and the microcirculation, which could contribute, at least in part, to the pathophysiology of hypertension. One hypothesis is that insulin might accelerate the vascular complications in subjects with hyperinsulinemia. On the other hand, it was demonstrated that the reduced membrane fluidity of erythrocytes was associated with lower plasma nitric oxide (NO) and higher asymmetric dimethyl arginine (ADMA) levels. Furthermore, the lower the plasma adiponectin levels, the lower the membrane fluidity of erythrocytes.In this context, it is strongly suggested that abnormalities in membrane function and their regulation by vasoactive substances might contribute, at least in part, to the pathophysiology of hypertension and the metabolic syndrome.

为了评估代谢综合征中的膜异常，我们研究了代谢综合征受试者中血管活性物质对膜流动性的影响。膜流动性是生物膜的一种物理化学性质，是微循环调节的重要因素。应用电子顺磁共振和自旋标记技术，观察了高血压合并肥胖和糖尿病患者红细胞膜流动性的变化。结果表明，血浆胰岛素水平越高，红细胞膜流动性越低。提示高胰岛素血症可能参与红细胞膜流动性的调节。红细胞膜流动性的降低可能引起血液流变学行为和微循环的紊乱，这至少部分地参与了高血压的病理生理过程。一种假说是胰岛素可能加速高胰岛素血症受试者的血管并发症。另一方面，研究表明红细胞膜流动性降低与血浆一氧化氮（NO）水平降低和不对称二甲基精氨酸（ADMA）水平升高有关。此外，血浆脂联素水平越低，红细胞膜流动性越低，在这种情况下，这是强烈建议，在膜功能的异常和血管活性物质的调节可能有助于，至少部分，高血压和代谢综合征的病理生理。