CaィイD12+ィエD1-Metabolism and Membrane Functions in Hypertension

CaiD12+IeD1-高血压的代谢和膜功能

• 批准号: 10670674
• 负责人: TSUDA Kazushi
• 金额: $ 1.79万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670674/
• 关键词: Hypertension; β-Endorphin; Norepinephrine; Acetylcholine; Membrane fluidity; Adrenomedullin; Calcium; Dual energy X-ray Absorptiometry; 尿中Ca排泄量; vitamin D; 腎; Ca-balance; 神経伝達物質; acetylcholine; 細胞膜流動性; adrenomedullin; cAMP

The purpose of the present study was to determine the role of Ca and other intrinsic factors in the pathogenesis if hypertension.β-Endorphin significantly inhibited the stimulation-evoked norepinephrine (NE) release in rat medulla oblongata. The effect of β-endorphin was more attenuated in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto(WKY) rats. The finding shows that β-endorphin might actively participate in the regulation of sympathetic nerve activity in hypertension. Additionally, we examined the of dopamine D2 receptors in acetylcholine (ACh) release in the central nervous system. Exogenously applied dopamine and apomorpine reduced the simulation-evoked ACh release. The activity of the dopamine D2 receptors in SHR was significantly more attenuated that in WKY rats. The results showed that the dopamine D2 receptors might have a potential role in the regulation of cholinergic nerve activity in hypertension.In the next series of the experiments, we studied th … More e changes in membrane fluidity of erythrocytes in patients with essential hypertension (EH) by means of an electron paramagnetic resonance (EPR) method. The erythrocyte membrane fluidity was lower in EH than in normotensive subjects. Adrenomedullin(AM) significantly increased the membrane fluidity of erythrocytes. The effect of AM was potentiated by prostaglandin E1and dibutyryl cAMP. Furthermore, AM increased the membrane fluidity to a greater extent in EH than in normotensive subjects. The results showed that AM might be involved in the regulation of cell function in hypertension.Recent studies have documenbted abnormalities in Ca-metabolism at systemic level in human hypertension as well as in experimental hypertension. Since bone is the largest store of Ca in the body, we investigated the bone mineral density (BMD) in patients with EH by means of the dual energy X-ray absorptiometric (DXA) method. DXA analysis showed a significant decrease in BMD in female EH compared with age-matched normotensive subjects. In addition , the BMD was inversely correlated with systolic blood pressure. Furthermore, the greater the urinary Ca-excretion, the lower the BMD in females. The results of the present study demonstrate the DXA provided an index of whole Ca-balance, and suggest that hypertension might be associated with reduced BMD in female EH. Less

本研究的目的是确定Ca和其他内在因素在高血压发病机制中的作用。β-内啡肽显着抑制大鼠延髓刺激诱发的去甲肾上腺素（NE）释放。 β-内啡肽的作用在自发性高血压大鼠（SHR）中比在正常血压 Wistar-Kyoto（WKY）大鼠中更减弱。研究结果表明，β-内啡肽可能积极参与高血压交感神经活动的调节。此外，我们还检测了中枢神经系统中乙酰胆碱 (ACh) 释放中多巴胺 D2 受体的变化。外源性应用多巴胺和阿扑吗啡减少了模拟诱发的乙酰胆碱释放。 SHR 中多巴胺 D2 受体的活性比 WKY 大鼠中明显减弱。结果表明，多巴胺D2受体可能在高血压胆碱能神经活动的调节中具有潜在作用。在接下来的一系列实验中，我们通过电子顺磁共振（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低于血压正常者。肾上腺髓质素（AM）显着增加红细胞膜的流动性。前列腺素 E1 和二丁酰 cAMP 增强了 AM 的作用。此外，与血压正常的受试者相比，AM 在 EH 中更大程度地增加了膜的流动性。结果表明AM可能参与高血压细胞功能的调节。最近的研究已经证明人类高血压以及实验性高血压在全身水平上存在钙代谢异常。由于骨骼是体内最大的钙储存库，我们通过双能 X 射线骨密度测定 (DXA) 方法研究了 EH 患者的骨矿物质密度 (BMD)。 DXA 分析显示，与年龄匹配的血压正常受试者相比，女性 EH 的 BMD 显着下降。此外，BMD与收缩压呈负相关。此外，尿钙排泄量越大，女性的骨密度越低。本研究的结果表明，DXA 提供了整体钙平衡的指数，并表明高血压可能与女性 EH 的 BMD 降低有关。较少的

项目成果

津田和志,西尾一郎,増山善明: "延髄内norepinephrine release調節機序におけるcAMP-dependent protein kinase(PKA)の役割と高血圧での意義について"臨床薬理.. (in press).

Kazushi Tsuda、Ichiro Nishio、Yoshiaki Masuyama：“cAMP 依赖性蛋白激酶 (PKA) 在调节髓内去甲肾上腺素释放中的作用及其在高血压中的意义”临床药理学（出版中）。

Tsuda K, Kinoshita Y, Nishino I, Masuyama Y: "Adrenomedullin and membrane fluidity of erythrocytes in mild essentila hypertension"J Hypertens. 17. 201-210 (1999)

Tsuda K、Kinoshita Y、Nishino I、Masuyama Y：“轻度高血压中的肾上腺髓质素和红细胞膜流动性”J Hypertens。

津田和志,西尾一郎,増山善明: "ラット視床下部内Norepinephrine Releaseに対するNeuropeptide Yの作用とSodium Ionの影響について"Therapeutic Researh. 20. 1383-1387 (1999)

Kazushi Tsuda、Ichiro Nishio、Yoshiaki Masuyama：“神经肽 Y 和钠离子对大鼠下丘脑去甲肾上腺素释放的影响”治疗研究 20。1383-1387 (1999)。

津田和志 他: "中枢神経内Acetylcholine Releaseに及ぼすCa Channel Blocker(VerapamilならびにNicardipine)の影響について." 臨床薬理. 29. 187-188 (1998)

Kazushi Tsuda 等人：“Ca 通道阻滞剂（维拉帕米和尼卡地平）对中枢神经系统乙酰胆碱释放的影响。”29. 187-188 (1998)。

Tsuda K, Tsuda S, Nishio I, Masuyama Y, Goldstein M: "Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats"Am J Hypertens. 11. 1475-1479 (1998)

Tsuda K、Tsuda S、Nishio I、Masuyama Y、Goldstein M：“甘丙肽对正常血压和自发性高血压大鼠中枢神经系统多巴胺释放的影响”Am J Hypertens。