SODIUM-INDUCED HYPERTENSION AND THE ENDOGENOUS DIGITALISLIKE FACTOR OF THE HYPOTHALAMIC ORIGIN

钠诱发的高血压和下丘脑起源的内源性数码样因子

• 批准号: 05671927
• 负责人: TAKAHASHI Hakuo
• 金额: $ 1.41万
• 依托单位: KANSAI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671927/
• 关键词: SODIUM; HYPERTENSION; OUABAIN; DIGITALIS GYLCOSIDE; HYPOTHALAMUS; ADRENAL

The sensitive ELISA for ouabain has been developed to measure the very low level of endogenous ouabainlike factors (OLF). The level of the sensitivity was pg/well order by the use of catalyzed reporter deposition to amplify the optical density. When the urine sample was assayd by this ELISA system, urinary excretion of OLF was markedly elevated in DOCA-salt hypertensive rats as compared to the control rats. The tissue distribution of the OLF was also examined ; it was high in the pituitary, the adrenal and the hypothalamus in this decreasing order. In support of this, immunohistochemical study by the monoclonal antibody for ouabain revealed that the neuron containing OLF was restricted in the hypothalamic paraventricular nuclei and the supraoptic nuclei and the fibers distributed around the circumventricular organs of the third ventricle, and that the immunoreactivity existed in the adrenal medulla too. To explore the possible involvement of the central monoaminergic neurons in the release of OLF from the hypothalamus, 6-hydroxydopamine (OHDA) was given intracerebroventricularly. Six-OHDA significantly reduced the plasma level of OLF,which was accompanied by the similar reduction of OLF content in the pituitary and the hypothalamus but not in the adrenal. Therefore, it was suggested that the plasma OLF was of the hypothalamic origin, but not of the adrenal. The implication of OLF in the human hypertension was also investigated ; regular mild exercise decreased blood pressure significantly, which was accompanied by the significant reduction in plasma levels of OLF.These findings indicate that OLF has been playing significant roles in blood pressure regulation even in human essential hypertension.

开发出灵敏的哇巴因 ELISA 检测方法，用于测量极低水平的内源性哇巴因样因子 (OLF)。通过使用催化报告沉积来放大光密度，灵敏度水平为pg/孔级。当通过该 ELISA 系统检测尿液样本时，与对照大鼠相比，DOCA-盐高血压大鼠的 OLF 尿液排泄量显着升高。还检查了 OLF 的组织分布；垂体、肾上腺和下丘脑的含量依次递减。哇巴因单克隆抗体的免疫组织化学研究表明，含有OLF的神经元仅限于下丘脑室旁核和视上核以及第三脑室室周器官周围分布的纤维，并且肾上腺髓质中也存在免疫反应性。为了探索中枢单胺能神经元在下丘脑释放 OLF 过程中的可能参与，脑室内给予 6-羟基多巴胺 (OHDA)。六-OHDA显着降低血浆OLF水平,同时伴随着垂体和下丘脑中OLF含量的类似降低,但肾上腺中OLF含量没有降低。因此，有人认为血浆OLF源自下丘脑，而非肾上腺。还研究了 OLF 在人类高血压中的影响；规律的轻度运动可显着降低血压，同时伴随着血浆OLF水平的显着降低。这些发现表明，OLF甚至在人类原发性高血压中在血压调节中发挥着重要作用。

项目成果

Takahashi H.et al.: "Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats." Hypertension Research. 18. 319-324 (1995)

Takahashi H.et al.：“慢性抑制大鼠一氧化氮诱发高血压的机制。”

Takahashi H. et al.: "Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats." Hypertension Research. 18. 319-324 (1995)

Takahashi H. 等人：“慢性抑制大鼠一氧化氮诱发高血压的机制。”

Y.Komiyama,et al.: "Production of ouabain-like factors of hypothalamo-pituitary origin, determined by a sensitive ELISA for ouabain,is increased in DOCA-salt hypertensive rats" Pathophysiology. (in press).

Y.Komiyama 等人：“通过对哇巴因的敏感 ELISA 测定，下丘脑-垂体来源的哇巴因样因子的产生在 DOCA 盐高血压大鼠中增加”病理生理学。

Takahashi H. et al.: "Digoxin-like immunoreativity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance." Journal of Cardiovascular Pharmacology. 22. S22-S24 (1993)

Takahashi H. 等人：“地高辛样免疫反应性可能导致葡萄糖不耐受患者的高胰岛素血症相关高血压。”

H.Takahashi1),Y.Terano2): "Ouabainlike immunoreactive materials in the hypothalamus and the adrenal medulla are increased in DOCA‐salt hypertensive rats" Proceedings on the Symposium on Sodiumpump. (in press). (1994)

H.Takahashi1)、Y.Terano2)：“DOCA 盐高血压大鼠下丘脑和肾上腺髓质中的哇巴因样免疫反应物质增加”钠泵研讨会论文集（正在出版）。