Ca^<2+>-Metabolism and Hypertension

本研究旨在探讨高血压患者Ca^<2+>和Na^+-代谢的异常。神经肽Y （NPY）显著抑制大鼠延髓和下丘脑刺激诱发的去甲肾上腺素（NE）释放。百日咳毒素（一种有效的gi蛋白抑制剂）的预处理减弱了NPY对NE释放的抑制作用。随着灌注介质钠浓度的增加，NPY对NE释放的抑制作用明显减弱。这一发现提示，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，我们还研究了Ca^<2+>通道阻滞剂地尔硫卓和蛋白激酶C （PKC）抑制剂对高血压患者中枢乙酰胆碱（ACh）释放的影响。地尔硫卓抑制刺激诱发的大鼠纹状体[^3H]乙酰胆碱释放呈剂量依赖性。抑制作用在大鼠SHR的纹状体中比在WKY的纹状体中更为明显。PKC抑制剂H-7也比WKY大鼠更大程度地减少刺激诱发的[^3H]乙酰胆碱释放。结果表明，Ca^<2+>-PKC系统在高血压神经递质释放调控中的作用增强。在接下来的一系列实验中，我们利用电子顺磁共振（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患者的红细胞膜流动性明显低于血压正常者。红细胞的Ca^<2+>负荷降低了细胞膜的流动性。在EH中Ca^<2+>引起的流动性变化与年龄相关。与正常血压对照组相比，Na^+， K^+- atp酶抑制剂瓦巴因也在更大程度上降低了EH的膜流动性。另一方面，胰岛素降低了红细胞的膜流动性。Ca^<2+>通道阻断剂地尔硫卓可拮抗胰岛素，而Ca^<2+>通道阻断剂地尔硫卓可增强胰岛素的作用。根据这些结果，我们认为Ca^<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