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

Research Project

Project/Area Number 60570403
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

TAKAHASHI Hakuo  Second Department of Internal Medicine, Kyoto Prefectural University of Medicine, 医学部, 助手 (80094431)

Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥900,000 (Direct Cost: ¥900,000)
KeywordsHypertension / digitalis-like substance / hypothalamus / sodium salt / angiotensin II / 副腎 / 食塩 / 交感神経活動
Research Abstract

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

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Hakuo Takahashi: Journal of Hypertension. 4(Suppl). s317-s320 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: Journal of Hypertension. 4(Suppl). s156-s159 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: Japanese Circulation Journal. 51. 1199-1207 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: American Journal of Hypertension. 1. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: American Journal of Hypertension. 1. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: "Centrally-induced vasopressor responses to ouabain in DOCA-salt hypertensive rats" Cardiovascular Research. 21. 439-446 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: "Evidence for a digitalis-like substance in the hypothalamo-pituitary axis in rats" Journal of Hypertension. 4(Suppl.). s317-s320 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: "Augmented vasodepressor and sympathetic responses to intracerebroventricular injections of diltiazem, a calcium channel blocker, in DOCA-salt hypertensive rats" Journal of Hypertension. 4(Suppl.). s156-s159 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: "Evidence for a digitalis-like substance in the hypothalamopituitary axis in rats; Implications in the central cardiovascular regulation associated with an excess intake of sodium" Japanese Circulation Journal. 51. 1199-1207 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi: Centrally-induced vasopressor responses to Na, K-ATPase inhibitors in hypertensive rats. Elsevier Science Publisher B.V., 371-376 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hakuo Takahashi et al.: Journal of Hypertension.

    • Related Report
      1986 Annual Research Report
  • [Publications] Hakuo Takahashi et al.: Japanese Circulation Journal.

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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