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-ATPase抑制剂已被证明随着钠负荷的增加而增加，因此它是钠尿第三因子的候选者之一。由于抑制血管Na，K-ATPase导致外周血管阻力增加，洋地黄样物质一定参与了高血压的发生。结果表明，地高辛样免疫反应物(DLI)在垂体、下丘脑、肾上腺等器官中含量最高。侧脑室注射秋水仙碱后，下丘脑DLI含量增加，血浆浓度降低，支持该物质在下丘脑产生的观点。高钠饲料喂养2周后，DLI排尿量明显增加。此外，抗地高辛抗体免疫组织化学显示…DLI胞体分布于室旁核和视上核，纤维分布于正中隆起、终板血管器和穹隆下器。损毁AV3V区可通过减少尿中DLI和Na，K-ATPase抑制剂的排泄量来减轻DOCA-盐性高血压的发展，提示脑内DLI参与了高血压的发生发展。为了探讨DLI的释放机制，我们反复脑室注射生理盐水、胺、多肽和前列腺素。只有高渗盐水使血浆浓度升高，而血管紧张素受体拮抗剂的同时输注可使血浆浓度降低。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可能参与了高血压、肾性高血压和激素性高血压的发病机制。较少

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