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Effects of calcium antagonists on vascular endothelial, smooth muscle and sympathetic nerve functions

Research Project

Project/Area Number 08670107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionSHIGA UNIVERSITY OF MEDICAL SCIENCE

Principal Investigator

OKAMURA Tomio  SHIGA UNIVERSITY OF MEDICAL SCIENCE,Faculty of Medicine Department of Pharmacology Associate Professor, 医学部, 助教授 (70152337)

Co-Investigator(Kenkyū-buntansha) AYAJIKI Kazuhide  SHIGA UNIVERSITY OF MEDICAL SCIENCE,Faculty of Medicine Department of Pharmacolo, 医学部, 助手 (10167968)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsCalcium antagonist / EDRF / Nitric oxide / Nitroxidergic nerve / Flunarizine / Cyclic GMP / Calcium / calmodulin-dependent protein kinase / Noradrenaline / 血管内皮由来弛緩因子(EDRF) / 血管緊張性調節 / 血管平滑筋 / 脳動脈
Research Abstract

Effects of calcium antagonists on the mechanical responses of isolated dog artery strips to the direct vasoconstrictor (prostaglandin F_<2alpha>), EDRF releaser (substance P) and nerve stimulation were examined. Contraction induced by prostaglandin F_<2alpha> was inhibited by nicardipine (L-type calcium channnel inhibitor), flunarizine and AE0047 (a new dihydropyridine derivative), but not by omega-conotoxin (N-type channel inhibitor). Endothelium-dependent relaxation caused by substance P was not suppressed by nicardipine, omega-conotoxin nor tetramethrin (T-type channel inhibitor). Perivascular nerve stimulation produced relaxations in the cerebral artery whereas contractions in the mesenteric artery ; the relaxation and contraction were abolished by nitric oxide (NO) synthase inhibitors and alpha-adrenoceptor antagonists, respectively, indicating that neurotransmitters mainly released from the cerebral and mesenteric arteries are NO and noradrenaline, respectively. Nicardipine and t … More etramethrin did not affect the neurogenic relaxation in the cerebral artery, but omega-conotoxin, flunarizine and AE0047 inhibited the relaxation. Although contractions induced by nerve stimulation and noradrenaline were suppressed by both AE0047 and nicardipine, noradrenaline release caused by nerve stumulation was not inhibited by nicardipine but by AE0047. Cadmium, a non-selective calcium antagonist, inhibited the mechanical responses to prostaglandin F_<2alpha>, substance P and nerve stimulation. These results indicate that calcium influx is mainly regulated by L-type channel in the vascular smooth muscles and by N-type channel in the perivascular nerves, but that in the endothelial cells has not been determined since specific L-, N- and T-type calcium channel inhibitors failed to inhibit the calcium-dependent endothelial function. Suppression by flunarizine, but not by nicardipine, of the neurogenic cerebroarteial relaxation may explain its anti-migraine action. Further, it is found that some of the new dehydropyridine derivatives possess not only direct vasodilator action but also inhibitory action on sympathetic nerve function. Involvement of calcium/calmodulin-dependent protein kinase II in the production of neural NO has also been suggested. Less

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Toda, N.: "Nitroxidergic nerve : regulation of vascular tone and blood flow in the brain" Journal of Hypertension. 14・4. 423-434 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toda, N.: "Effect of Ca^<2+>/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation." European Journal of Pharmacology. 340・1. 59-65 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ayajiki K.: "Flunarizine,an anti-migraine agent,impairs nitroxidergic nerve function in cerebral arteries." European Journal of Pharmacology. 329・1. 49-53 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 戸田 昇: "NO産生とカルシウム拮抗薬" 血管と内皮. 8・1. 34-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endoh, M.: "Molecular and Cellular Mechanisms of Cardiovascular Regulation" Springer-Verlag Tokyo, 452 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toda, N., Nitroxidergic nerve: "regulation of vascular tone and blood flow in the brain." Journal of Hypertension. 14/4. 423-434 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toda, N.: "Effect of Ca^<2+>/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation." European Journal of Pharmacology. 340/1. 59-65 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ayajiki K: "Flunarizine, an anti-migraine agent, impairs nitroxidergic nerve function in cerebral arteries." European Journal of Pharmacology. 329/1. 49-53 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toda, N: "NO production and calcium antagonists. (in Japanese)" Blood Vessel & Endothlium. 8/1. 34-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endoh, M: Molecular and Cellular Mechanisms of Cardiovascular Regulation. Springer-Verlag, 452 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toda,N.: "Effect of Ca^<2+>/ calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation." European Journal of Pharmacology. 340・1. 59-65 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ayajiki K.: "Flunarizine,an anti-migraine agent,impairs nitroxidergic nerve function in cerebral arteries." European Journal of Pharmacology. 329・1. 49-53 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 戸田 昇: "NO産生とカルシウム拮抗薬" 血管と内皮. 8・1. 34-39 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Toda: "Nitroxidergic nerve:regulation of vascular tone and blood flow in the brain" Journal of Hypertension. 14・4. 423-434 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Toda: "Neurogenic nitric oxide (NO) in the regulation of cerebroarterial tone" Journal of Chemical Neuroanatomy. 10・3,4. 259-265 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Okamura: "Neural mechanism of pressor action of nitric oxide synthase inhibitor in anesthetized monkeys." Hypertension. 28・3. 341-346 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Okamura: "Canine retinal arterial and arteriolar dilatation induced by nipradilol,a possible glaucoma therapeutic" Pharmacology. 53. 302-310 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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