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Modulation of intracellular Ca ion concentrations by endothelium-derived hyperpolarizing factor in vascular smooth muscle

Research Project

Project/Area Number 04454150
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionNagoya City University Medical School

Principal Investigator

SUZUKI Hikaru  Nagoya City University Medical School, Professor, 医学部, 教授 (80037548)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Yoshimichi  Nagoya City University Medical School, Assistant Professor, 医学部, 助手 (80145755)
福田 裕康  名古屋市立大学, 医学部, 研究員
三輪 恭子  名古屋市立大学, 医学部, 研究員
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsEndothelium-derived hyperpolarizing factao / Vascular smooth muscle / Calcium
Research Abstract

(1) Vascular smooth muscles for the measurement of intracellular Ca ion concentrations and also for mechanical responses were successfully prepared in the guinea-pig aorta. Smooth muscle of this artery was confirmed to be relaxd by EDHF.
(2) Endothelial cells isolated from bovine thoracic aorta using enzymatic dispersion were cultured on microcarrier beeds. Preliminary experiments showed that these cells (3x10^7 cells/each experiment) can produce several types of vasoactive substance in response to bradikinine (Bk).
(3) Production of EDHF from the cultured endothelial cells was estimated by using isolated thoracic aortic ring of the guinea-pig. Superfusates of the cultured endothelial cells with Bk relaxd the Bk-contracted aortic ring preparations, and the relaxation was resistant to nitroarginine and indomethacin, but sensitive to high-K solution containing nitroaginine. The results suggested that Bk stimulates the cultured endothelial cells to release vesorelaxtant factors which may be … More different from EDRF or PG12. The effects of these unidentified factors reduced in high-K solution, indicated an involvement of membrane hyperpolarization.
4. Intracellular Ca ion concentrations modulated by EDHF were estimated from the fluorescent intensities of Ca-sensitive dye, Fura-2 loaded in primary cultured smooth muscle cells of the guinea-pig aorta (Fura-2 was loaded into the cell in a form of Fura-2 AM). Bk elevated the fluorescent transiently to level equivalent to 300-500nM Ca from the resting level of about 50nM, and them reached the steady level of about 200nM.Bk-containing superfusate elluted from the cultured endothelial cells reduced the Fura-2 fluorescent to the resting level, irrespective to the absence and presence of nitroarginine and indonethacin. The reduction of fluorescent intensity by the endothelial effluents was not clearly detected in high-K solution. The results suggested that hyperpolarization by endothelial factor may be responsible to the reduction of fluorescent. Thus, EDHF relax arterial smooth muscles with reduced Ca concentrations. Less

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 鈴木光: "Nitroarginine-sensitive and insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery." Japanese Journal of Physiology. 42. 335-347 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 鈴木光: "内皮細胞由来過分極因子" 日本平滑筋学会誌. 28. 225-227 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 鈴木光: "EDHF" 現代医療. 25. 161-162 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 鈴木光: "内皮細胞由来血管弛緩因子" Therapeutic Research. 14. 49-53 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 章国良: "Vasodilation induced by substance P in the guinea pig carotid artery." American Journal of Physiology. (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] Suzuki, H.Chen, G., Yamamoto, Y., & Miwa, K.: "Nitroaginine-sensitive and insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery" Japanese Journal of Physiology. 42. 335-347 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yamamoto, Y., Chen, G., Miwa, K., & Suzuki, H.: "Permeablity and mg-blockage of histamine-operated cation channel in endothelial cells of rat intrapulmonary artery" Journal of Physiology, London. 450. 395-408 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Suh, Sh., Xue, L., Zhang, G., Yamamoto, Y., & Suzuki, H: "Inhibitory actions of mci-154 on guinea-pig mesenteric artery and vein preparations" European Journal Of Pharmacology. 219. 377-383 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Miyahara, H., Inayama, S., Hori, Y., & Suzuki, H.: "Vascular responses induced by topical application of steroid in the ear artery" General Pharmacology. 24. 1155-1162 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Suzuki, H., Chen, G., & Yamamoto, Y.: "Endothelium-derived hyperpolarizing factor" Japanese Circulation Journal. 56. 170-174 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Suzuki, H.: "Endothelium-dependent hyperpolarization of smooth muscle" Journal Of Smooth Muscle Research. 28. 225-227 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohno, N., Ito, KM., Yamamoto, Y., & Suzuki, H.: "Suramin selectively inhibitory junction potential in the guinea-pig stomach" European Journal Of Pharmacology. 249. 121-123 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Itoh, T., Ito, S., Shafiq, J, & Suzuki, H: "Effects of a newly synthesized k channel opener, y-26763, on noradrenaline-induced Ca mobilization in smooth muscle of the rabbit mesenteric artery" British Journal Of Pharmacologyy. 111. 165-172 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Zhng, G., Yamamoto, Y., Miwa, K., & Suzuki, H.: "Vasodilation induced by substance p in the guinea-pig carotid artery" American Journal Of Physiology. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Suzuki, H: "Endothelium-derived vasodilators" Therapeutic Research. 14(8). 15-18 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 鈴木光: "Nitroarginine-sensitive and insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery." Japanese Journal of Physiology. 42. 335-347 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 鈴木光: "内皮細胞由来過分極因子" 日本平滑筋学会誌. 28. 225-227 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 鈴木光: "EDHF" 現代医療. 25. 161-162 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 鈴木光: "内皮細胞由来血管弛緩因子" Therapeutic Research. 14. 49-53 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 章国良: "Vasodilation induced by substance P in the guinea pig carotid artery." American Journal of Physiology. 印刷中. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 鈴木,光: "内皮細胞由来平滑筋過分極因子" Journal of Smooth Muscle Research. 28. 225-227 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suzuki,H.,Chen,G. and Yamamoto,Y.: "Endothelium-derived hyperpolarizing factor(EDHF)" Japanese Circulation Journal. 56. 170-174 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 鈴木 光: "内皮細胞由来血管弛緩因子" Therapeutic Research. 14. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 鈴木 光・山本 喜通、章 国良: "EDHF" 現代医療. 25. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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