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

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着钠负荷的增加而增加，它是钠尿的第三个候选因素之一。由于血管Na， k - atp酶的抑制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）的含量在垂体、下丘脑、肾上腺和其他器官中依次高。经脑室注射秋水仙碱后，下丘脑DLI含量增加，血浆浓度降低，支持该物质产生于下丘脑的观点。高钠饮食2周后大鼠DLI尿量明显增加。抗地高辛抗体免疫组化证实含有DLI的细胞体主要分布在室旁核和视上核，纤维主要分布在正中隆起、终板血管器官和皮质下器官。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 -盐性高血压的发展，表明大脑中的DLI参与了高血压的发展。为了研究DLI的释放机制，反复注射生理盐水、胺、肽和前列腺素。只有高渗盐水使血药浓度升高，而同时输注血管紧张素拮抗剂则使血药浓度降低。在原发性高血压和肾性高血压患者中，血浆DLI浓度与血压显著相关。这些结果表明，下丘脑洋地黄样物质肯定参与了原发性、肾性和类固醇性高血压的发病机制。少

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