FUNDAMENTAL STUDIES ON THE HYPOTHALAMIC DIGITALIS-LIKE SUBSTANCE

下丘脑洋地黄样物质的基础研究

• 批准号: 02807228
• 负责人: TAKAHASHI Hakuo
• 金额: $ 0.9万
• 依托单位: KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807228/
• 关键词: ENDOGENOUS DIGITALIS-LIKE SUBSTANCE; INSULIN RESISTANCE; SODIUM; HYPERTENSION; CENTRAL NERVOUS SYSTEM; IMMUNOHISTOCHEMISTRY; ナトリウム利尿ホルモン; ジギタリス様物質; 脈管作動性物質

Mechanism of Releases of Endogenous Digitalis-like Substance(EDLF):When hypertonic saline was infused intracerebroventricularly, the plasma level of digoxin-like immunoreactivity (DLI) elevates. In the present study, we found that intravenous infusions of saline caused elavation of plasma DLI. Hypertonic saline did not have additional effects on the regular saline. Therefore, the central effects of sodium could be one of mechanisms, and the elevation of central venous pressure could be the other. On the chronic condition of sodium-loading, however, sodium may affect the central nervous system to release the DLI since sodium concentration in the cerebrospinal fluid elevates with the sodium-loading.Immunohistochemical Study:When the brain tissue was examined with anti-digoxin antibody, we found that the DLI exists in the cell body of the paraventricular and supraoptic nuclei, and their fibers distributed in the periventricular organs such as OVLT and SFO, and median eminence. Some of the … More DLI containing cells also contained vasopressin and/or oxytocin. It was also found in the posterior pituitary. In the Kidneys, the faint immunoreactivity was found at the tubular epithelial cells.Relationship Between EDLF and Insulin Resistance: The interest has been focussed on the insulin resistance as the pathogenesis of hypertension, diabetes, hyperlipidemia and atherosclerosis. Because insulin increases renal sodium absorption, we thought that EDLF may be increased as the cause of hypertension. As the results, serum insulin levels significanty correlated not only with blood pressure, but also with plasma DLI concentrations. When the partial F ratio of insulin was calculated with a multiple regression analysis against blood pressure, it was the greatest in the borderline group, and was not achieve the significant level in a diabetic group.Conclusion: When insulin levels are elevated and promoted sodium reabsorption, EDLF is released from the hypothalamus particularly in the borderline diabetic group. In the diabetic group, other mechanisms than insulin is responsible for the elevation of blood pressure. Less

内源性洋地黄样物质（EDLF）释放机制：侧脑室灌注高渗盐水后，血浆地高辛样免疫反应性（DLI）水平升高。在本研究中，我们发现静脉输注生理盐水可引起血浆DLI升高。高渗盐水对常规盐水没有额外影响。因此，钠的中枢作用可能是机制之一，中心静脉压升高可能是另一个机制。在慢性钠负荷状态下，钠可影响中枢神经系统释放DLI，因为脑脊液中的钠浓度随钠负荷而升高。免疫组织化学研究：用地高辛抗体检测脑组织，发现DLI存在于室旁核和视上核的胞体中，其纤维分布于室周器官如OVLT、SFO和正中隆起。一些 ...更多信息 含有DLI的细胞还含有加压素和/或催产素。它也被发现在垂体后叶。EDLF与胰岛素抵抗的关系：胰岛素抵抗作为高血压、糖尿病、高脂血症和动脉粥样硬化的发病机制，一直受到人们的关注。由于胰岛素增加肾脏钠吸收，我们认为EDLF增加可能是高血压的原因。结果表明，血清胰岛素水平不仅与血压呈显著正相关，而且与血浆DLI浓度呈显著正相关。当用多元回归分析计算胰岛素的偏F比率时，临界组最大，而在糖尿病组中未达到显著水平。结论：当胰岛素水平升高并促进钠重吸收时，EDLF从下丘脑释放，特别是在临界糖尿病组中。在糖尿病组中，胰岛素以外的其他机制是导致血压升高的原因。少

项目成果

Hakuo Takahashi, Manabu Yoshimura: "Renal factors in hypertension" Gardioangiology. 31. 145-151 (1992)

Hakuo Takahashi，Manabu Yoshimura：“高血压的肾脏因素”Gardioangiology。

高橋 伯夫: "インスリン耐性による高血圧発症機序" Therapeutic Research. 12. 2022-2025 (1991)

高桥郁夫：“胰岛素抵抗诱发高血压的机制”治疗研究12。2022-2025（1991）。

Masato NIshimura,Hakuo Takahashi,Makoto Matsusawa,Iwao Ikegaki,Tadasi Nakanishi,Manabu Yoshimura: "The effects of insulin and insulinーlike materials in the brain on central cardiovascular regulation:with special reference to the central effects of sodium

Masato Nishimura、Hakuo Takahashi、Makoto Matsusawa、Iwao Ikegaki、Tadasi Nakanishi、Manabu Yoshimura：“大脑中胰岛素和胰岛素样物质​​对中枢心血管调节的影响：特别参考钠的中枢作用