Ca^<2+>-Metabolism and Hypertension

本研究旨在探讨高血压患者Ca^+、Na^+代谢的异常。神经肽Y（NPY）可显著抑制刺激诱发的大鼠延髓和下丘脑去甲肾上腺素（NE）释放。百日咳毒素（一种有效的Gi蛋白抑制剂）预处理可减弱NPY对NE释放的抑制作用。当灌流液中钠浓度增加时，NPY对NE释放的抑制作用明显减弱。这一发现表明，钠离子可能积极参与调节NPY介导的中枢神经系统功能。此外，我们还观察了Ca^<2+>通道阻断剂地尔硫卓和蛋白激酶C（PKC）抑制剂对高血压中枢乙酰胆碱（ACh）释放的影响。地尔硫卓以剂量依赖的方式抑制刺激诱发的大鼠纹状体[^3H] ACh释放，抑制作用在纹状体中更明显。 ...更多信息 SHR大鼠纹状体的神经元密度明显高于WKY大鼠。与WKY大鼠相比，PKC抑制剂H-7也能更大程度地减少SHR刺激诱发的[^3H]ACh释放。本实验用电子顺磁共振（EPR）方法研究了原发性高血压（EH）患者红细胞膜流动性的变化。EH患者红细胞膜流动性明显低于正常人。红细胞内Ca^<2+>负荷降低了膜流动性。Ca^<2+>诱导的高血压患者膜流动性的改变与年龄有关。Na^+，K^+-ATP酶抑制剂哇巴因也能使高血压患者膜流动性降低，其程度大于正常血压对照组。另一方面，胰岛素降低红细胞膜流动性。Ca^<2+>可增强胰岛素的作用，而Ca^<2+>通道阻断剂地尔硫卓可拮抗胰岛素的作用。从这些结果，我们得出结论，钙^<2+>代谢异常可能积极参与高血压的发病机制。少

The purpose of the present study was to investgate the abnormalities in the Ca^<2+>-and Na^+-metabolism in hypertension. Neuropeptide Y (NPY) significantly inhibited the stimulation-evoked norepinephrine (NE) release in rat medulla oblongata and hypothalamus. Pretreatment of pertussis toxin (a potent inhibitor of the Gi-proteins) attenuated the suppressive effects of NPY on NE release. When the sodium concentration of the perfusion medium was increased, the inhibitory effect of NPY on NE release was significantly reduced. The finding suggests that sodium ions might actively participate in regulating the NPY-mediated functions in the central nervous system. In addition, we examined the effects of Ca^<2+> channel blocker diltiazem and protein kinase C (PKC) inhibitor on central acetycholine (ACh) release in hypertension. Diltiazem inhibited the stimulation-evoked [^3H] ACh release in rat striatum in a dose-dependent manner.The inhibitory effect was significantly more pronounced in the st … More riatum of SHR than in the striatum of WKY rats. The PKC inhibitor H-7 also reduced the stimulation-evoked [^3H]ACh release to a greater extent in SHR than WKY rats. The results show the enhanced Ca^<2+>-PKC system in the regulation of neurotransmitter release in hypertension.In the next series of the experiments, we studied the changes in membrane fluidity of erythrocytes in patients with essential hypertension (EH) by means of an electron paramagnetic resonance (EPR) method. The erythrosyte membrane fluidity was significantly lower in patients with EH than in normotensive subjects. The Ca^<2+>-loading to erythrocytes decreased the membrane fluidity. The Ca^<2+>-induced change in the fluidity was correlated with age in EH.Ouabain, the Na^+, K^+-ATPase inhibitor, also reduced the membrane fluidity to a greater extentin EH than in the normotensive controls. On the other hand, insulin decreased the membrane fliuidity of erythrocytes. The effect of insulin was potentiated by Ca^<2+>, and, by contrast, was antagonized by the Ca^<2+>channel blocker diltiazem. From these results, we conclude that abnormalities in the Ca^<2+>-metabolism might actively participate in the pathogenesis of hypertension. Less