Membrane Functions and Hypertension

膜功能与高血压

• 批准号: 05670631
• 负责人: TSUDA Kazushi
• 金额: $ 1.28万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670631/
• 关键词: Hypertension; Membrane function; Signal transduction; Neurotransmitter release; Excitatory amino acid; Peptide hormone; Membrane fluidity; Electron paramagnetic resonance; 赤血球; インスリン; カルシウム; 糖尿病; 運動療法; 細胞膜異常; 中枢神経系; 神経伝達物質; Norepinephrine

In the first series of experiments, we describe the results of studies regarding the effects of excitatory amino acids and peptide hormones on neurotransmitter release in the central nervous system of hypertension. The excitatory aino acid, l-glutamate (L-Glu), significantly increased the release of norepinephrine (NE) and acetylcholine (ACh) in rat central nervous system. The effect of L-Glu was potentiated by glycine, and, by contrast, was antagonized by Mg^<2+> and MK-801. The finding suggests that L-Glu might increase the release of NE and ACh, partially mediated by N-methyl-D-aspartate receptors in the central nervous system. On the other hand, neuropeptide Y (NPY) inhibited the stimulation-evoked NE release in rat striatum. A part of the mechanisms might be explained by interactions with presynaptic D2-receptors and the pertussis toxin-sensitive Gi-proteins. Bradykinin increased the stimulation-evoked NE release from rat hypothalamus. The bradykinin-effect might be partially due … More to the facilitation of Ca^<2+> influx through the dihydropyridine-sensitive Ca^<2+> channels in the brain. In spontaneously hypertensive rats (SHR), the effects of L-Glu, NPY and bradykinin were altered compared with age-matched Wistar-Kyoto rats. These results suggests that the excitatory amino acids and peptide hormones might be involved in the regulation of neural activities in hypertension.In the second series of experiments, we examined changes in membrane fluidity of erythrocytes in patients with essential hypertension by means of an electron paramagnetic resonance (EPR) method. The membrane fluidity of erythrocytes was significantly lower in patients with essential hypertension than in the normotensive controls. The decrease in the fluidity was pronounced in the subjects with a family history of hypertension. Insulin significantly decreased the membrane fluidity of erythrocytes. The insulin-effect was potentiated by Ca^<2+>. From these results, we have drawn the conclusion that abnormalities in membrane functions and their related signal transduction systems might actively participate in the pathogenesis of hypertension. Less

在第一系列的实验中，我们描述了兴奋性氨基酸和肽类激素对高血压中枢神经系统神经递质释放的影响的研究结果。兴奋性氨基酸L-谷氨酸（L-Glu）能显著增加大鼠中枢神经系统去甲肾上腺素（NE）和乙酰胆碱（ACh）的释放。甘氨酸可增强L-谷氨酸的作用，而Mg^<2+>和MK-801则可拮抗L-谷氨酸的作用。这一发现表明，L-Glu可能增加NE和ACh的释放，部分通过N-甲基-D-天冬氨酸受体介导的中枢神经系统。另一方面，神经肽Y（NPY）抑制刺激诱发的大鼠纹状体NE释放。部分机制可能是通过与突触前D2受体和百日咳毒素敏感的Gi蛋白的相互作用来解释的。缓激肽增加刺激诱发的大鼠下丘脑NE释放。缓激肽效应可能部分是由于 ...更多信息 通过脑内二氢吡啶敏感的Ca^2+通道促进Ca^2+内流。与年龄匹配的Wistar-Kyoto大鼠相比，在自发性高血压大鼠（SHR）中，L-Glu、NPY和缓激肽的作用发生了改变。这些结果表明，兴奋性氨基酸和肽类激素可能参与了高血压神经活动的调节。在第二系列实验中，我们用电子顺磁共振（EPR）方法检测了原发性高血压患者红细胞膜流动性的变化。原发性高血压患者红细胞膜流动性明显低于正常对照组。有高血压家族史的受试者的流动性明显降低。胰岛素显著降低红细胞膜流动性。Ca^<2+>可增强胰岛素效应。结果提示，细胞膜功能及其相关信号转导系统的异常可能积极参与了高血压的发病过程。少

项目成果

Tsuda K, Tsuda S, Nishio I et al.: "Effects of nicardipine on the release of acetylcholine in the rat central nervous system" Japanese Circulation Journal. 57. 993-999 (1993)

Tsuda K、Tsuda S、Nishio I 等人：“尼卡地平对大鼠中枢神经系统乙酰胆碱释放的影响”日本循环杂志。

Tsuda K, Tsuda S, Goldstein M et al.: "Effects of bradykinin on [^3H] norepinephrine release in rat hypothalamus" Clinical and Experimental Pharmacology and Physiology. 20. 787-791 (1993)

Tsuda K、Tsuda S、Goldstein M 等人：“缓激肽对大鼠下丘脑 [^3H] 去甲肾上腺素释放的影响”临床和实验药理学和生理学。

Tsuda K, Nishio I, Masuyama Y: "Membrane fluidity of erythrocytes and its modulation by ouabain in essential hypertension" Free Radical Research Communications. 19(suppl). S163-S169 (1993)

Tsuda K、Nishio I、Masuyama Y：“红细胞膜流动性及其在原发性高血压中乌本苷的调节”自由基研究通讯。

Tsuda K,Minatogawa Y,Kido R et al.: "Genetic influences on membrane fluidity of erythrocytes in essential hypertension-an electron paramagnetic resonance study-" Magnetic Resonance in Medicine. 6. 167-169 (1995)

Tsuda K、Minatokawa Y、Kido R 等人：“原发性高血压中红细胞膜流动性的遗传影响 - 电子顺磁共振研究 -”医学中的磁共振。

Tsuda K, Tsuda S, Nishio I et al.: "Glutamatergic regulation of [^3H] -noradrenaline release in the medulla oblongata of normotensive and spontaneously hypertensive rats" Journal of Hypertension. 12. 517-522 (1994)

Tsuda K、Tsuda S、Nishio I 等人：“正常血压和自发性高血压大鼠延髓中 [^3H]-去甲肾上腺素释放的谷氨酸调节”高血压杂志。