Ca^<2+>-Metabolism and Hypertension

Ca^<2 >-代谢与高血压

• 批准号: 08670819
• 负责人: TSUDA Kazushi
• 金额: $ 1.22万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670819/
• 关键词: Hypertension; Protein kinase C; Neurotransmitter release; Membrane Fluidity; Calcium; Sodium; Insulin; Electron paramagnetic resonance; 高インスリン血症; 赤血球膜; 細胞膜機能; Ca^<2+>代謝; protein kinase C; insulin

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

本研究旨在探讨高血压病患者钙、钠代谢的异常。神经肽Y(NPY)可显著抑制刺激诱发的去甲肾上腺素(NE)在大鼠延髓和下丘脑的释放。百日咳毒素(胃肠道蛋白的有效抑制剂)可减弱NPY对去甲肾上腺素释放的抑制作用。当灌流液中钠离子浓度增加时，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中枢神经系统中NPY介导的功能。此外，我们还观察了钙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性乙酰胆碱(ACh)释放的影响。地尔硫卓以剂量依赖方式抑制刺激诱导的大鼠纹状体[~(3 H)]ACh释放，抑制作用在st…更为明显SHR纹状体多于WKY大鼠纹状体。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[~(3 H)]ACh释放。实验结果表明，高血压患者红细胞膜流动性的变化主要是通过增强的Ca~(2+)~(2+)-PKC系统实现的。EH患者红细胞膜流动性明显低于正常血压者。红细胞膜上的钙离子负载量降低了膜的流动性。Na~(2+)，K~(2+)-ATPase抑制剂哇巴因对EH膜流动性的影响与增龄有关，对EH膜流动性的降低幅度大于正常血压对照组。另一方面，胰岛素降低了红细胞膜的流动性。钙通道阻滞剂地尔硫卓可增强胰岛素的作用，而钙通道阻滞剂地尔硫卓则拮抗胰岛素的作用。提示钙代谢异常可能积极参与高血压的发病机制。较少

项目成果

Tsuda K et al.: "The role of sodium-potassium adenosine triphosphatase in the regulation of membrane fluidity of erythrocytes in spontaneously hypertensive rats." American Journal of Hypertension. 10. 1411-1414 (1997)

Tsuda K 等人：“钠钾三磷酸腺苷酶在调节自发性高血压大鼠红细胞膜流动性中的作用。”

Tsuda K,Yoshikawa A,Nishio I and Masuyama Y: "Aerobic physical exercise and membrane functions of erythrocytes in mild essential hypertension." Hypertension. 28. 547 (1996)

Tsuda K、Yoshikawa A、Nishio I 和 Masuyama Y：“轻度原发性高血压中的有氧运动和红细胞膜功能”。

Tsuda K,Nishio I and Masuyama Y: "The role of calcium-protein kinase C systems in the regulation of acetylcholine release in the central nervous system of spontaneously hypertensive rats." Japanese Heart Journal. 37. 532 (1996)

Tsuda K、Nishio I 和 Masuyama Y：“钙蛋白激酶 C 系统在调节自发性高血压大鼠中枢神经系统乙酰胆碱释放中的作用。”

Tsuda K et al.: "Modulation of[^3H]dopamine release by neuropeptide Y in rat striatal slices." European Journal of Pharmacology. 321. 5-11 (1997)

Tsuda K 等人：“神经肽 Y 在大鼠纹状体切片中调节 [^3H] 多巴胺释放。”

Tsuda K et al.: "Glutamatergic regulation of[^3H]acetylcholine release in striatal slices of normotensive and spontaneously hypertensive rats." Neurochemistry International. 29. 231-238 (1996)

Tsuda K 等人：“正常血压和自发性高血压大鼠纹状体切片中[^3H]乙酰胆碱释放的谷氨酸调节。”