Abnormalities in Membrane Signal Transduction in Hypertension

在第一系列实验中，我们描述了评价多肽激素对高血压患者去甲肾上腺素(NE)释放的影响的研究结果。神经肽Y(NPY)和甘丙素(Gal)抑制刺激诱发的大鼠下丘脑和延髓去甲肾上腺素的释放。部分机制可能是通过与突触前α2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)也能抑制大鼠脑NE的释放。降钙素基因相关肽的作用可能部分是由于阻断了中枢神经系统二氢吡啶敏感的钙通道的钙内流。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)。这些结果提示，多肽激素可能参与了高血压中枢神经系统交感神经张力的调节。在第二系列实验中，我们用电子自旋共振(ESR)和自旋标记的方法研究了高血压患者红细胞膜流动性的变化。SHR和高血压病患者红细胞膜流动性明显低于正常血压对照组。高血压病患者膜流动性降低与血浆内源性洋地黄样因子有关。哇巴因负载红细胞膜流动性降低。与正常血压对照组相比，哇巴因引起的改变在高血压患者中显著。从这些发现，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。

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.