Abnormalities in Membrane Signal Transduction in Hypertension

在第一个系列的实验中，我们描述了评估肽激素对高血压患者去甲肾上腺素（NE）释放影响的研究结果。神经肽Y （NPY）和甘丙肽（Gal）抑制刺激诱导的大鼠下丘脑和延髓释放NE。部分机制可能与突触前α 2-肾上腺素能受体和百日咳毒素敏感的gi蛋白相互作用有关。降钙素基因相关肽（CGRP）也能抑制NE从大鼠脑释放。cgrp效应的部分原因可能是通过中枢神经系统中对二氢吡啶敏感的Ca^<2+>-通道阻断Ca^<2+>-内流。在自发性高血压大鼠（SHR）中，NPY、Gal和CGRP的作用明显小于Wistar Kyoto大鼠（WKY）。这些结果提示肽激素可能参与高血压病患者中枢神经系统交感神经张力的调节。在第二个系列的实验中，我们通过电子自旋共振（ESR）和自旋标记方法检查了高血压患者红细胞膜流动性的变化。SHR患者和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。原发性高血压患者膜流动性降低与血浆内源性地黄样因子有关。红细胞负荷瓦巴因使细胞膜流动性降低。高血压患者与正常对照组相比，瓦阿因引起的改变明显。由此我们得出结论，信号转导和膜特征的异常可能积极参与了高血压的发病过程。

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.