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Abnormalities in Membrane Signal Transduction in Hypertension

高血压膜信号转导异常

基本信息

批准号：
02670405
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：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

In the first series of the experiments, we describe the results of studies to evaluate the effects of peptide hormones on norepinephrine (NE) release in hypertension. Neuropeptide Y (NPY) and galanin (Gal) inhibited stimulation-evoked NE release from hypothalamus and medulla oblongata of rats. A part of the mechanisms might be explained by interactions with presynaptic alpha2-adrenergic receptors and the pertussis toxin-sensitive Gi-proteins. Calcitonin gene-related peptide (CGRP) also inhibited NE release from rat brain. The CGRP-effect might be partially due to blockade of Ca^<2+>-influx through dihydropyridine-sensitive Ca^<2+>-channels in the central nervous system. In spontaneously hypertensive rats (SHR), the effect of NPY, Gal and CGRP was significantly less than in Wistar Kyoto rats (WKY). These results suggest that the peptide hormones might be involved in the regulation of sympathetic tone in the central nervous system of hypertension.In the second series of the experiments, we examined alterations in membrane fluidity of erythrocytes in hypertension by means of an electron spin resonance (ESR) and spin labelling methods. The membrane fluidity of erythrocytes was significantly lower in SHR and in patients with essential hypertension than in the normotensive controls. The decrease in membrane fluidity in essential hypertension was correlated with endogenous digitalis-like factor in plasma. Ouabain-loading to erythrocytes decreased the membrane fluidity. The ouabain-induced change was pronounced in hypertension compared with normotensive controls. From these findings, we have drawn the conclusion that abnormalities in signal transduction and in membrane characteristics might actively participate in the pathogenesis of hypertension.

在第一系列的实验中，我们描述了研究结果，以评估肽类激素对高血压去甲肾上腺素（NE）释放的影响。神经肽Y（NPY）和甘丙肽（Gal）抑制刺激诱发的大鼠下丘脑和延髓NE释放。部分机制可能是通过与突触前α 2-肾上腺素能受体和百日咳毒素敏感的Gi蛋白的相互作用来解释的。降钙素基因相关肽（CGRP）也能抑制NE的释放。CGRP的作用可能部分是由于阻断了中枢神经系统中通过二氢吡啶敏感性Ca^<2 +>通道的Ca^<2 +>内流。在自发性高血压大鼠（SHR）中，NPY、Gal和CGRP的作用明显低于Wistar京都大鼠（WKY）。这些结果表明，肽类激素可能参与高血压中枢神经系统交感神经张力的调节.在第二系列的实验中，我们研究了高血压红细胞膜流动性的改变，通过电子自旋共振（ESR）和自旋标记方法。SHR和原发性高血压患者红细胞膜流动性明显低于正常对照组。原发性高血压时膜流动性降低与血浆内源性洋地黄样因子有关。哇巴因使红细胞膜流动性降低。与血压正常的对照组相比，哇巴因诱导的变化在高血压中是明显的。从这些发现中，我们得出结论，信号转导和膜特性的异常可能积极参与高血压的发病机制。