STUDIES ON THE BRAIN MECHANISM OF HYPERTENSION:THE ROLE OF THE HYPOTHALAMIC, ENDOGENOUS DIGITALIS-LIKE SUBSTANCE

高血压脑机制的研究：下丘脑内源性洋地黄样物质的作用

• 批准号: 60570403
• 负责人: TAKAHASHI Hakuo
• 金额: $ 1.09万
• 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: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570403/
• 关键词: Hypertension; digitalis-like substance; hypothalamus; sodium salt; angiotensin II; 副腎; 食塩; 交感神経活動

Excessive intake of sodium is believed to be involved in the pathogenesis of essential hypertension. Because the digitalis-like Na, K-ATPase inhibitor has been demonstrated to increase with sodium-loading, it is one of candidates of the third factor of natriuresis. Because inhibition of vascular Na, K-ATPase leads to increased peripheral vascular resistance, the digitalis-like substance must be implicated in the hypertension. We have demonstrated that the content of the digoxin-like immunoreactivity (DLI) is high in the pituitary, hypothalamus, adrenal and the other organs in this order. And the content of DLI in the hypothalamus increased and plasma concentration decreased when colchicine was injected intracerebroventricularly (ICV), which supported the idea that the substance is produced in the hypothalamus. The urinary output of the DLI markedly increased when the rats were fed with a high sodium diet for 2 weeks. Furthermore, immunohistochemistry with antidigoxin antibody demonstra … More ted that the DLI containing cell bodies are distributed in the paraventricular nucleus and supraoptic nucleus, and those fibers distributed in the median eminence, organum vasculosum of the laminae terminalis and subfornical organ. Electrical lesions of the AV3V area attenuated the development of DOCA-salt hypertension by decreasing the urinary output of both the DLI and Na, K-ATPase inhibitor, suggesting that the DLI in the brain is involved in the development of hypertension. To investigate the releasing mechanism of DLI, ICV injections of saline, amines, peptides and prostaglandins are repeated. Only the hypertonic saline increased the plasma concentration, which were abolished by the concomitant infusions of angiotensin antagonists. In both essential hypertensives and renal hypertensive patients, plasma concentrations of the DLI correlated with the blood pressure significantly. These results indicate that the hypothalamic digitalis-like substance is surely involved in the pathogenesis of essential, renal and steroid-induced hypertension. Less

钠的过量摄入被认为与原发性高血压的发病机制有关。由于洋地黄样Na，K-ATP酶抑制剂已被证明随钠负荷增加而增加，因此它是促钠排泄的第三因子的候选者之一。由于抑制血管Na，K-ATP酶导致外周血管阻力增加，洋地黄样物质必然与高血压有关。我们已经证明，地高辛样免疫反应性（DLI）的含量高，在垂体，下丘脑，肾上腺和其他器官在这个顺序。侧脑室注射秋水仙碱后，下丘脑DLI含量增加，血浆DLI浓度降低，支持了该物质在下丘脑产生的观点。高钠饮食2周后，DLI的尿量明显增加。此外，抗地高辛抗体免疫组化显示， ...更多信息 结果表明，DLI的胞体分布于室旁核和视上核，DLI的纤维分布于正中隆起、终板血管器和穹窿下器。AV3V区的电损伤通过减少DLI和Na，K-ATP酶抑制剂的尿量来减弱DOCA盐高血压的发展，表明脑中的DLI参与高血压的发展。为了研究DLI的释放机制，重复ICV注射生理盐水、胺、肽和洋地黄素。只有高渗盐水增加了血浆浓度，同时输注血管紧张素拮抗剂可消除血浆浓度。在原发性高血压和肾性高血压患者中，DLI的血浆浓度与血压显著相关。这些结果表明，下丘脑洋地黄样物质确实参与了原发性高血压、肾性高血压和激素性高血压的发病机制。少

项目成果

Hakuo Takahashi: Journal of Hypertension. 4(Suppl). s156-s159 (1986)

高桥白夫：高血压杂志。

Hakuo Takahashi: Journal of Hypertension. 4(Suppl). s317-s320 (1986)

高桥白夫：高血压杂志。

Hakuo Takahashi: Centrally-induced vasopressor responses to Na, K-ATPase inhibitors in hypertensive rats. Elsevier Science Publisher B.V., 371-376 (1986)

Hakuo Takahashi：高血压大鼠对 Na、K-ATP 酶抑制剂的中枢诱导血管升压反应。

Hakuo Takahashi: Japanese Circulation Journal. 51. 1199-1207 (1987)

高桥白夫：日本流通杂志。

Hakuo Takahashi: "Inhibitory roles of the hypothalamic atrial natriuretic polypeptide on the vasopressin release in the sodium-loaded rats" Biochemical and Biophysical Research Communications. 139. 1285-1291 (1986)

Hakuo Takahashi：“下丘脑心房钠尿多肽对钠负荷大鼠加压素释放的抑制作用”生物化学和生物物理研究通讯。