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CaィイD12+ィエD1-Metabolism and Membrane Functions in Hypertension

Research Project

Project/Area Number 10670674
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionWakayama Medical College

Principal Investigator

TSUDA Kazushi  Wakayama Medical College, Division of Cardiology, Department of Medicine, Assistant Professor, 医学部, 講師 (90217315)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHypertension / β-Endorphin / Norepinephrine / Acetylcholine / Membrane fluidity / Adrenomedullin / Calcium / Dual energy X-ray Absorptiometry / 尿中Ca排泄量 / vitamin D / 腎 / Ca-balance / 神経伝達物質 / acetylcholine / 細胞膜流動性 / adrenomedullin / cAMP
Research Abstract

The purpose of the present study was to determine the role of Ca and other intrinsic factors in the pathogenesis if hypertension.β-Endorphin significantly inhibited the stimulation-evoked norepinephrine (NE) release in rat medulla oblongata. The effect of β-endorphin was more attenuated in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto(WKY) rats. The finding shows that β-endorphin might actively participate in the regulation of sympathetic nerve activity in hypertension. Additionally, we examined the of dopamine D2 receptors in acetylcholine (ACh) release in the central nervous system. Exogenously applied dopamine and apomorpine reduced the simulation-evoked ACh release. The activity of the dopamine D2 receptors in SHR was significantly more attenuated that in WKY rats. The results showed that the dopamine D2 receptors might have a potential role in the regulation of cholinergic nerve activity in hypertension.
In the next series of the experiments, we studied th … More e changes in membrane fluidity of erythrocytes in patients with essential hypertension (EH) by means of an electron paramagnetic resonance (EPR) method. The erythrocyte membrane fluidity was lower in EH than in normotensive subjects. Adrenomedullin(AM) significantly increased the membrane fluidity of erythrocytes. The effect of AM was potentiated by prostaglandin E1and dibutyryl cAMP. Furthermore, AM increased the membrane fluidity to a greater extent in EH than in normotensive subjects. The results showed that AM might be involved in the regulation of cell function in hypertension.
Recent studies have documenbted abnormalities in Ca-metabolism at systemic level in human hypertension as well as in experimental hypertension. Since bone is the largest store of Ca in the body, we investigated the bone mineral density (BMD) in patients with EH by means of the dual energy X-ray absorptiometric (DXA) method. DXA analysis showed a significant decrease in BMD in female EH compared with age-matched normotensive subjects. In addition , the BMD was inversely correlated with systolic blood pressure. Furthermore, the greater the urinary Ca-excretion, the lower the BMD in females. The results of the present study demonstrate the DXA provided an index of whole Ca-balance, and suggest that hypertension might be associated with reduced BMD in female EH. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Tsuda K, Kinoshita Y, Nishino I, Masuyama Y: "Adrenomedullin and membrane fluidity of erythrocytes in mild essentila hypertension"J Hypertens. 17. 201-210 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K, Tsuda S, Nishiro I, Masuyama Y: "The release of acetylcholine and its dopominergic regulation in the central nervous system of spontaneously hypertensive rats"J Cardiovasc Pharmacol. 34(suppl. 4). 553-557 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K, Tsuda S, Nishio I, Masuyama Y, Goldstein M: "Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats"Am J Hypertens. 11. 1475-1479 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K, Tsuda S, Nishio I, Masuyama Y, Goldstein M: "Captopril inhibits both dopaminergic and cholinergic reurotransmission in the central nervous system"Clin Exp Pharmacol physiol. 25. 904-907 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 津田和志,木下幸子,西尾一郎,増山善明: "電子スピン共鳴よりみた本態性高血圧の細胞膜機能に及ぼすインスリンならびにグルコースの影響について"臨床薬理. 30. 397-398 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 津田和志,西尾一郎,増山善明: "ラット視床下部内Norepinephrine Releaseに対するNeuropeptide Yの作用とSodium Ionの影響について"Therapeutic Researh. 20. 1383-1387 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K., Kinoshita Y., Nishio I., Masuyama Y: "Adrenomedullin and membrane fluidity of erythrocytes in mild essential hypertension."J Hypertens. 17. 201-210 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K., Tsuda S., Nishio I., Masuyama Y: "The release of acetylcholine and its dopominergic regulation in the central nervous system of spontaneously hypertensive rats."J Cardiovasc Pharmacol. 34 (suppl.4). S53-S57 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimura K., Tsuda K., Sasajima H., Shiotani M., Baba A., Hano T., Nishio I: "Arterial relaxation mediated by endothelium-derived hyperpolarizing factor in hypertension induced by chronic inhibition of nitric oxide synthesis."Clin Exp Hypertens. 7. 1203-1221 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K., Tsuda S., Nishio I., Masuyama Y., goldstein M: "effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats."Am J Hypertens. 11. 1475-1479 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K., Tsuda S., Nishio I., Masuyama Y., Goldstein M: "Captopril inhibits both dopaminergic and cholinergic neurotransmission in the central nervous system."Clin Exp Pharmacol Physiol. 25. 904-907 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuda K,Kinoshita Y,Nishio I,Masuyama Y: "Adrenomedullin and membrane fluidity of erythrocytes in mild essential hypertension"J Hypertens.. 17. 201-210 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuda K,Tsuda S,Nishio I,Masuyama Y: "The release of acetylcholine and its dopominergic regulation in the central nervous system of spontaneously hypertensive rats"J Cardiovasc Pharmacol.. 34(Suppl.4). S53-S57 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 津田和志,西尾一郎,増山善明: "Neuropeptide Y(NPY)遺伝子"日本臨床.(2000年増刊号 高血圧 上巻). 58(2000年増刊号). 580-583 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 津田和志,木下幸子,西尾一郎,増山善明: "電子スピン共鳴よりみた本態性高血圧の細胞膜機能に及ぼすインスリンならびにグルコースの影響について"臨床薬理.. 30. 397-398 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 津田和志,西尾一郎,増山善明: "ラット視床下部内Norepinephrine Releaseに対するNeuropeptide Yの作用とSodium Ionの影響について"Therapeutic Research.. 20. 1383-1387 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 津田和志,西尾一郎,増山善明: "延髄内norepinephrine release調節機序におけるcAMP-dependent protein kinase(PKA)の役割と高血圧での意義について"臨床薬理.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuda K et al.: "Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats." American Jouranl of Hypertension. 11. 1475-1479 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuda K et al.: "Captopril inhibits both dopaminergic and cholinergic neurotransmission in the central nervous system." Clinical and Experimental Pharmacology and Physiology.25. 904-907 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 津田和志 他: "電子スピン共鳴よりみた老年者本態性高血圧患者の細胞膜Fluidityとその調節因子に関する検討." Therapeutic Research. 19. 1551-1554 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 津田和志 他: "中枢神経内Acetylcholine Releaseに及ぼすCa Channel Blocker(VerapamilならびにNicardipine)の影響について." 臨床薬理. 29. 187-188 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 津田和志 他: "中枢神経内Acetylcholine Release調節におけるCa^<2+>-protein kinase C系の役割と高血圧における意義について." 心臓. 30(suppl2). 68-71 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 津田和志 他: "新しい降圧薬 総論2)高血圧症の治療の進歩." 医薬ジャーナル. 34. 66-71 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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