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Multiple mechanisms for vasodilator effect of magnesium

Research Project

Project/Area Number 03454249
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

FUJITA Toshiro  The University of Tokyo, Associate Professor, The Fourth Department of Internal, 医学部(分), 助教授 (10114125)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Katsutoshi  Clinical Stuff, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 医員
SHIMOSAWA Tatsuo  Clinical Stuff, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 医員 (90231365)
ANDO Katsuyuki  Associate, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 助手 (60184313)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥4,600,000 (Direct Cost: ¥4,600,000)
Keywordsmagnesium / vascular smooth muscle cells / vascular endothelial cells / vascular reactivity / sympathetic nervous system / angiotensin II / 高血圧 / 内皮依存性弛緩因子 / 中枢神経系 / バロファンクション / 内皮細胞 / 平滑筋細胞 / ノルエピネフリン
Research Abstract

Accumulating evidence suggests that deficiency of magnesium (Mg) not only cause hypertension but also accelerates its complication such as ischemic heart disease. These illness should be related to vascular effect of Mg. Mg has been demonstrated to directly dilate vasculature but might affect vascular tone indirectly through the other mechanisms so we examined the effect of Mg deficiency and excess on vascular endothelial and sympathetic nervous function.
(1) 7 week-old Sprague-Dawley (SD) rats was fed on low (3.27mg/100g) and high (87mn/100g) Mg diet for 4 weeks. Mg-deficient rats showed extremely low level of serum Mg compared with Mg-enriched rats. Systolic blood pressure was 130(〕SY.+-.〔)5 mmHg in Mg-dificient rats and 120(〕SY.+-.〔)3 mmHg in Mg-enriched rats (0.05<P<0.1). In intact aortic ring, Potassium (K)-induced contraction was not different between the two groups but maximal contraction (E_<max>) and pD_2 of norepinephrine (NE)-induced contraction was decreased in Mg-deficient … More rats. Endothelial denudation normalized pD_2 of Mg-deficient rats but no E_<max>. Thus, vascular reactivity is suppressed in Mg-deficient rats, which may compensate for the rise in blood pressure due to Mg-deficiency. This effect may at least party be mediated through endothelial function.
(2) We examined the effect of extracellular magnesium on vascular sympathetic nerve activity using the perfusion system of isolated mesenteric artery of SD rats. Sympathetic activity was evaluated as pressor response and increased NE overflow by perivascular electrical stimulation. When Mg concentration in the perfusate was changed from 1.2 mM (normal level) to 0.3 mM, the responses of perfusion pressure and NE overflow by the electrical stimulation was enhanced. On the other hand, high(4.8 mM) Mg decreased it. Thus, Mg inhibits the vascular sympathetic nerve activity. Recently, several investigators including us demonstrated that angiotensin II(ANGII) enhanced the peripheral sympathetic activity. Increased Mg concentration of perfusate, however, suppressed the ANGII-induced enhancement of the sympathetic nervous system. Because ANGII is locally generated in vasculature (for example, endothelial cells), Mg may modify the sympathetic activity through indirect mechanism such as effect on endothelial function as well as its direct action.
In summary, Mg modifies vascular tone through not only the direct action on vascular smooth muscle but also the indirect ones via endothelial cells and sympathetic nerve. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] 藤田 敏郎: "Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium." Hypertension. 20. 466-472 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 藤田 敏郎: "Salt loads attenuate pottasium-induced vasodilation of of forearm vasculature in human." Hypertension. 21. 772-778 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Possible role of sodium-hydrogen antiport in acetylcholine-induced relaxation of rat aorta" Biochemical and Biophysical Research Communication. 177. 407-413 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Antihypertensive effect of dieary calcium loading in angiotensin II-salt rats" American Journal of Physiology. 261. R1070-R1074 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Vasodilating actions of calcitonin gene-related peptide in normal man:Comparison with arterial natriuretic peptide" American Heart Journal. 123. 111-116 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Hemodynamic and endocrine changes associated with hypotensive action of amosulalol in essential hypertension." Journal of Cardiovascular Pharmacology. 20. 7-10 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Involvement of prostaglandins and renal hemodynamics in salt sensitivity of young spontaneously hypertensive rats." Journal of Hypertension. 11. 373-377 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Involvement of sympathetic nervous system in antihypertensive effect of cicletanine in salt-loaded young spontaneously hypertensive rats." American Journal of Hypertension. (印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 下沢 達雄: "Insulin inhibits norepinephrine overflow from peripheral sympathetic nerve endings." Biochemical and Biophysical Research Communication. 188. 330-335 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 下沢 達雄: "Enhancement of vasoconstrictor response by a non-calcemic analogue of vitamine D_3." Hypertension. 21. 253-258 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 高橋 克敏: "Tumor necrosis factor-α induces vascular hyporesponsiveness in Sprague-Dawley rats." Life Sciences. 50. 1437-1444 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 安東 克之: "Centrally mediated cardiovascular effects of taurine.(in Cental Neural Mechanisms in Cardiovascular Regulation)" George Knous,John Ciriello, 10(102-112) (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fujita T., Sato Y.: "Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium" Hypertension. 20. 466-472 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fujita T., Ito Y.: "Salt loads attenuate potassium-induced vasodilation of forearm vasculature in human" Hypertension. 21. 772-778 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Sato Y., Ito Y., Ogata E., Fujita T.: "Effect of salt loading on aldosterone response to long-term angiotensin II in rays" Journal of Cardiovascular Pharmacology. 17. 386-389 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Takahashi K., Ono A., Shimosawa T., Ogata E., Fujita T.: "Possible role of sodium-hydrogen antiport in acetylcholine-induced relaxation of rat aorta" Biochemical and Biophysical Research Communication. 177. 386-389 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Sato Y., Ono A., Takahashi K., Shimosawa T., Ogata E., Fujita T.: "Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats" American Journal of Physiology. 261. R1070-R1074 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Ito Y., Ogata E., Fujita T.: "Vasodilating actions of calcitonin gene-related peptide in normal man : the comparison with atrial natriuretic peptide" American Heart Journal. 123. 111-116 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Noda H., Ogata E., Fujita T.: "Hemodynamic and endocrine changes associated with hypotensive action of amosulalol in essential hypertension" Journal of Cardiovascular Pharmacology. 20. 7-10 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Ono A., Sato Y., Asano S., Fujita T.: "Involvement of prostaglandins and renal hemodynamics in salt sensitivity young spontaneously hypertensive rats" Journal of Hypertension. 11. 373-377 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ando K., Ono A., Sato Y., Asano S., Fujita T.: "Involvement sympathetic nervous system in antihypertensive effect of cicletanine in salt-loaded young spontaneously hypertensive rats" American Journal of Hypertension. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimosawa T., Ando K., Ono A., Takahashi K., Isshiki M., Kanda M., Ogata E., Fujita T.: "Insulin inhibits norepinephrine overflow from peripheral sympathetic nerve endings" Biochemical and Biophysical Research Communication. 188. 330-335 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimosawa T., Ando K., Fujita T.: "Enhancement of vasoconstrictor response by non-calcemic analogue of vitamin D_3" Hypertension. 21. 253-258 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi K., Ando K., Ono A., Shimosawa T., Ogata E., Fujita T.: "Tumor necrosis factor-alpha induces vascular hyporesponsiveness in Sprague-Dawley rats" Life Sciences. 50. 1437-1444 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 藤田 敏郎: "Salt laods attenuate potassium-induced vasodilation of forearm vasculature in human." Hypertension. 21. 772-778 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 安東 克之: "Involvement of prostaglandins and renal hemodynamics in salt sensitivity of young spontaneously hypertensive rats." Journal of Hypertension. 11. 373-377 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 安東 克之: "Involvement of sympathetic nervous system in antihypertensive effect of cicletanine in salt-loaded young spontaneously hypertensive rats." American Journal of Hypertension. (発表予定).

    • Related Report
      1993 Annual Research Report
  • [Publications] 安東 克之: "Vasodilating actions of calcitonin gene-related peptide in normal man: comparison with atrial natriuretic peptide." American Heart Journal. 123. 111-116 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高橋 克敏: "Tumor necrosis factor-α induces vascular hyporesponsiveness in Sprague-Dawley rats." Life Sciences. 50. 1437-1444 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 安東 克之: "Hemodynamic and endocrine changes associated with hypotensive action of amosulalol in essential hypertension." Journal of Cardiovascular Pharmacology. 20. 7-10 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 藤田 敏郎: "Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium" Hypertension. 20. 466-472 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 下澤 達雄: "Insulin inhibits norepine phrine overflow from peripheral sympathetic nerve endings." Biochemical and Biophysical Research Communication. 188. 330-335 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 安東 克之: "Centrally mediated cardiovascular effects of taurine.(Central neural mechanisms in cardiovascular regulation.)" George Knous,John Ciriello., 488(102-112) (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 佐藤 雄二,尾形 悦郎,藤田 敏郎: "Role of chlroide in angiotensin IIーinduced saltーsensitive hypertension" Hypertension. 18. 622-629 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 佐藤 雄二,安東 克之,尾形 悦郎,藤田 敏郎: "High potassium intake attenuates antihyperensive response to air stress in DOCAーsalt rats" Am J Physiol. 260. R941-R945 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 安東 克之,高橋 克敏,小野 歩,下澤 達雄,尾形 悦郎,藤田 敏郎: "Possible role of sodiumーhydrogen antiport in acetylcholineーinduced relaxation of rat aorta" Biochem Biophys Res Comm. 177. 407-413 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 安東 克之,佐藤 雄二,小野 歩,高橋 克敏,下澤 達雄,尾形 悦郎,藤田 敏郎: "Antihypertensive effect of dieary calcium loadind in angiotensin IIーsalt rats" Am J Physiol. 261. R1070-R1074 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 安東 克之,伊東 康,尾形 悦郎,藤田 敏郎: "Vasodilating actions of calcitonin geneーrelated peptide in normal man:Comparison with arterlal natriuretic peptide" Am Heart J. 123. 111-116 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 岡崎 具樹,安東 克之,五十嵐 徹也,尾形 悦郎,藤田 敏郎: "The conserved mechanism of negative gene regulation by extracellular calciumーparaathyroid hormone gene versus atrial natriーuretic polypeptide gene" J Clin Invest.

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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