Membrane Functions and Hypertension

在第一个系列的实验中，我们描述了关于兴奋性氨基酸和肽激素对高血压中枢神经系统神经递质释放影响的研究结果。兴奋性氨基酸l-谷氨酸（L-Glu）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。甘氨酸能增强L-Glu的作用，而Mg^<2+>和MK-801则能拮抗L-Glu。提示L-Glu可能增加中枢神经系统n -甲基- d -天冬氨酸受体介导的NE和ACh的释放。另一方面，神经肽Y （NPY）抑制刺激诱发的纹状体NE释放。部分机制可以通过突触前d2受体和百日咳毒素敏感gi蛋白的相互作用来解释。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Ca^<2+>通过脑内对二氢吡啶敏感的Ca^<2+>通道流入的促进作用。在自发性高血压大鼠（SHR）中，与年龄匹配的Wistar-Kyoto大鼠相比，L-Glu、NPY和缓动素的作用发生了改变。这些结果提示，兴奋性氨基酸和肽激素可能参与高血压神经活动的调节。在第二个系列的实验中，我们通过电子顺磁共振（EPR）方法检测了原发性高血压患者红细胞膜流动性的变化。原发性高血压患者的红细胞膜流动性明显低于血压正常的对照组。在有高血压家族史的受试者中，流动性明显下降。胰岛素显著降低红细胞的膜流动性。Ca^<2+>可增强胰岛素效应。从这些结果，我们得出结论，膜功能及其相关信号转导系统的异常可能积极参与高血压的发病过程。少

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