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Physiological and pathophysiological roles of endothelium-derived hyperpotarizing factor in the control of organ perfusion.

Research Project

Project/Area Number 07307010
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY FACULTY OF MEDICINE

Principal Investigator

TAKESHITA Akira  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (30038814)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  KYUSYU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 助教授 (00235681)
NAKASHIMA Mikio  SAGA MEDICAL SCHOOL,ASSISTANT PROFESSOR, 助教授 (80159061)
ITOU Takeo  NAGOYA CITY UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (70159888)
SUZUKI Hikaru  NAGOYA CITY UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (80037548)
KANNO Morio  HOKKAIDOU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (00109422)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1995: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsEDHF / K channels / Nitric oxide / Microvessels / 血管内皮 / 内皮由来過分極因子(EDHF) / 一酸化窒素(NO) / 内皮依存性弛緩反応 / 内皮由来過分極因子 / 血管平滑筋
Research Abstract

1.Kanno et al. They found that acetylcholine-induced hyperpolarization is significantly reduced in streptozocin-induced diabetic rats and that lysophosphatidylcholine (LPC) impairs endothelium-dependent hyperpolarization in rats.
2.Suzuki et al. They demonstrated that EDHF activates two Ca^<2+>-activated K-channels in the guinea-pig arteriole and that endothelium-dependent hyperpolarizations are achieved by both EDHF and prostanoids in the guinea-pig coronary artery.
3.Itoh et al. They found that acetylcholine causes hyperpolarization via apaminsensitive K-channel in the rabbit middle cerebral artery and that non NO component largely contribute to the endothelium-dependent relaxation in rabbit microvessels.
4.Yui et al. They revealed that LPC inhibits endothelium-dependent hyperpolarization and non NO-and non PG12-dependent relaxations in the porcine coronary artery.
5.Shimokawa, Takeshita et al. They demonstrated that the importance of EDHF increases as the vessel size decreases in rats, rabbit, pigs, and humans and that estrogen and eicosapentaenoic acid improve both NO-mediated and EDHF-mediated relaxations in humans.
6.Fuji et al. They found that EDHF-mediated relaxations are reduced in spontaneously hypertensive rats (SHR) and that antihypertensive therapy, especially that with ACE inhibitors, improves the reduced responses in SHR.
7.Nakashima et al. They demonstrated that most of the inhaled anesthetics impair the EDHF-mediated relaxations and that vasoactive intestinal polypeptide may not be EDHF.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Fukao M et al: "Evidence for selective inhivition by lysophoshpatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric artery." Br J Pharmacol.116. 1541-1544. (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hashitani H, Suzuki H.: "K-channels which contribute to the acetylcholine-induced hyperpolarization in smooth muscle of the guinea-pig submucosal arteriole." J Physiol.501. 319-329 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimoto S, Itoh T.: "Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels." Eur J Pharmacol.330. 177-184 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eizawa H et al: "Iysophosphatidylcholine inhivits endothelium-dependent hyperpolarization and N^W-nitro-Larginine/indomethacin-resistant endothelium-dependent relaxation in the porcine coronary artery." Circulation.92. 3520-3526 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimokawa H et al.: "The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation." J Cardiovasc Pharmacol.28. 703-711 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onaka U et al.: "Antitypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats" Circulation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukao M et al.: "Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric artery." Br J Pharmacol.116. 1541-1544 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hashitani H,Suzuki H.: "K-channels which contribute to the acetylcholine-induced hyperpolarization in smoothe muscle of the guinea-pig submucosal arteriole." J Physiol.501. 319-329 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimoto S,Itoh T.: "Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels." Eur J Pharmacol.330. 177-184 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eizawa H et al.: "Lysophosphatidylcho line inhibits endothelium-dependent hyperpolarization and N^W-nitro-L-arginine/indomethacin-resistant endothelium-dependent relaxation in the porcine coronary artery." Circulation. 92. 3520-3526 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimokawa H et al.: "The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation." J Cardiovasc Pharmacol.28. 703-711 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onaka U et al.: "Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats." Circulation. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakashima M et al.: "Smooth muscle cell membrane hyperpolarization and relaxation of canine blood vessels to vasoactive intestinal polypeptide." J Cardiovasc Pharmacol.30. 273-277 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukao M et al: "Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric artery." Br J Pharmacol.116. 1541-1544. (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashitani H,Suzuki H.: "K-channels which contribute to the acetylcholine-induced hyperpolarization in smooth muscle of the guinea-pig submucosal arteriole." J Physiol.501. 319-329 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimoto S,Itoh T.: "Role of nitric oxide and nitric oxide-independent relaxing factor in contraction and relaxation of rabbit blood vessels." Eur J Pharmacol.330. 177-184 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Eizawa H et al.: "Lysophosphatidylcholine inhibits endothelium-dependent hyperpolarization and N^w-nitro-L-arginine/indomethacin-resistant endothelium-dependent relaxation in the porcine coronary artery." Circulation.92. 3520-3526 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimokawa H et al.: "The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation." J Cardiovasc Pharmacol.28. 703-711 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onaka U et al.: "Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats" Circulation. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimokawa H et al.: "The importance of the hyperpolarizing mechanism increases as the vessel size decreases…" Journal of Cardiovascular Pharmacology. 28. 703-711 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Urakami L et al.: "The importance of endothelium-derived hyperpolarizing factor in human arteries." Circulation. 94. I-636 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukao M et al.: "Structural differences in the ability of lysophospholipids to inhibit…" Biochem.biophysic.Res.Commun.227. 483-479 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oishi H et al.: "Chronic lead exposuremay inhibit endothelium-dependenthyperpolarizing factor in rats." Journal of Cardiovascular Pharmacology. 28. 558-563 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimokawa H et al.: "Endothelium and vascular injury in hypertension and atherosclerosis" In:Handbook of Hypertension,ed.by Zanchetti A.and Mancia G..(Elsevier,Amsterdam), 1007-1068 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki H et al.: "vasodilation induced by endothelium-derivedhyperpolarizing factor." In:Smooth Muscle Excitation,ed.by Bolton T.B.and Tomita T.(Academic Press,NY), 507-514 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimokawa H et al.: "Endothelium-dependent regulation of the cardiovascular system." Internal Medicine. 34. 939-946 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimokawa H et al.: "Significance of detective endothelial signal transduction in impaired endothelium-dependent relaxation in atherosclerosis" Gerontology. 41. 28-33 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukao M et al.: "Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization・・・・" Br J Pharmacol. 116. 1541-1543 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukao M et al.: "Thapsigargin- and cyclopiazonic acid-induced endothelium-dependent hyperpolarization in rat mesenteric artery." Br J Pharmacol. 115. 987-992 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe Y et al.: "Effect of membrane hyperpoiarization induced by a K^+ channel opener on histamine-induced Ca^<2+> mobilization・・・・" Br J Pharmacol. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Eizawa H et al.: "Lysophosphatidylcholine inhibits endothelium-dependent hyperpolarization and N^w-nitro-L-arginine/indomethacin・・・・" Circulation. 92. 3520-3526 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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