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Aging of cardiac conduction system

Research Project

Project/Area Number 09670086
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionHIROSAKI UNIVERSITY

Principal Investigator

MOTOMURA Shigeru  Hirosaki University, School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (40091756)

Co-Investigator(Kenkyū-buntansha) SEYA Kazuhiko  Hirosaki University, School of Medicine, Department of Pharmacology, Instructor, 医学部, 助手 (40281919)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsCardiac conduction system / Aging / CGMP / Canine isolated blood-perfused heart preparation / Microdialysis / Nitric Oxide / M2-muscarinic receptors / Tell II phosphodiasterase / イヌ血液還流房室結節標本 / cAMP / イヌ血液環流房室結節標本 / イヌ血液潅流房室結節標本
Research Abstract

To clear the mechanisms of the diseases of the cardiac conduction system, it is necessary to biochemically investigate the internal changes by aging of cardiac conduction system. However, there is no hypersensitive assay to assess the intracellular functions of cardiac conduction cells. The aims of this study are to develop the hypersensitive assay of substances concerning with the intracellular nitric oxide signaling system and to electrochemically assess the function of cardiac conduction system using canine isolated, blood-perfused heart preparation.
1. Development of the hypersensitive assay
1-1. Fluorometric assay of cGMP, which is important intracellular second messenger on the nitric oxide signalng system (Anal. Biochem., 1999).
1-2. Chemiluminescent assay of superoxide anion radicals, which are generated from the nitric oxide signaling system (Transplantation, 1999).
1-3. Chemiluminescent assay for hydroperoxide level of phosphatidylcholine hydroperoxide, which induce the conformat … More ional changes of cell membranes and cause the functional deterioration of receptors (J. Pharlnaceut. Biomed. Anal., 2000).
1-4. Myocardial interstitial norepinephrine measurement in the isolated, blood-perfused papillary muscle of dog using ex vivo microdialysis (J, Pharmacol. Toxicol. Methods, 2000). To know the myocardial interstitial norepinephrine concentration is important to assess the intracellular cAMP signaling system via β -adrenoceptors.
2. Electrochemical assessment of cardiac conduction system
2-1. We demonstrated that ONO-1 101 was a new ultrashort-acting β-adrenoceptor blocking drug by comparison with esmolol and propranolol using the canine isolated, blood-perfused heart preparations (J. Cardiovasc. Phanllacol., 1998)
2-2. By comparison of anti-M2 muscarinic effect of AF-DX 116 on atrioventricular nodal conduction with those of pirenzepine and atropine as antibradyarrhythmic drugs, we demonstrated that the muscarinic receptor subtype on the canine AV node is entirely of the M2-type, but only sparsely developed in the coronary vascular beds (J. Cardiovasc. Pharmacol., 1999).
2-3. By investigating the MCh-induced accentuated antagonism in the canine blood-perfused SA node, we demonstrated that MCh-induced accentuated antagonism in the SA node pacemaker activity can be modulated by endogeneous NO via an activation of the type II cyclic GMP-stimulated cyclic AMP phosphadiesterase (Am. J. Physiol., 2000). Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Mtomura S.,et al: "Time course of a new ultrashort-acting β-adrenoceptor blocking drug, ONO-1101 : Comparison with those of esmolol and Dropranolol by using the canine isolacted,blood-perfused heart preparations"J.Cardiovasc.Pharmacol. 31. 431-440 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Saya K.,et al: "Pharmacological properties of pteleprenine, a guinoline alkaloid extracted from Orixa Japanica, on guinea-Dig ileum and carine left atrium"J.Pharm.Pharmacol.. 50. 803-807 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lurie KG.,et al.: "Modulation of AV nodal and Hisian conduction by changes in extracelluar space"Am.J.Physiol.. 276. H953-H96* (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki S.,et al: "Comparison of anti-M2 muscarinic effect of AF-DX 116 on atrioventricular nodal conduction with those of pirenzepine and a tropine as anti brady arrhythmic drug"J.Cardiorasc.Pharmacol.. 33. 912-921 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motomura S.: "Differences in vascular selectivity of dihydro pyridine calcium antagonists when compared with their effects on respective intracardiac variahles"Hirosaki Med.J.. 51. S156-S163 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohkohchi N.,et al.: "Fragility of the electron transport chain and superoxide genera**** in mitochondria of the liver graft after cold ischemia"Transplantation. 67. 1173-1177 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K.,et al: "A fluorometric acsay for cyclic guanosine 3',5'-monophosphate incorporating a Sep-Pak cartridge and enzymatic cycling"Anal.Biochem.. 272. 243-249 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Daitoku K.,et al: "Cilinidipine suppresses DMPP-induced cardiac sympathetic nerve activation in canine blood-perfused papillary muscle"J.Cardiovasc.Pharmacol.. 34. S81-S84 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki S.,et al: "NO is involved in MCh-induced accentuated antagonism via typeII PDE in the canine blood-perfused SA node"Am.J.Physiol.. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K.,et al: "A chemiluminescent assay for hydroperoxide level of phosphatidylchsline hydroperoxide fraction purified by two Sep-Pak cartridges in hiological samples"J.Pharmaceut.Biomed.Anal_. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K.,et al: "Norepinephrine measurement in the isolated, blood-pertused papillary muscle of dog uding **vivo microdialysis"J.Pharmacol.Toxicol.Methods. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motomura H, Hagiwara A, Narumi Y, and Hashimoto K: "Time course of a new ultrashort-acting β-adrenoceptor blocking drug, ONO-1101 : Comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations"Journal of Cardiovascular Pharmacology. 31. 431-440 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K, Miki I, Murata K, Junke H, Motomura S, Araki T, Itoyama Y, and Oshima Y: "Pharmacological properties of pteleprenine, a quinoline alkaloid extracted from Orixa japonica, on guinea-pig ileum and canine left atrium"Journal of Pharmacy and Pharmacology. 50. 803-807 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lurie KC. Sugiyama A, McKnite S, Coffeen P, Hashimoto K. Motamura S: "Modulation of AV nodal and Hisian conduction by changes in extracellular space"American Journal of Physiology. 276. H953-H960 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki S, and Motomura S: "Comparison of anti-M2 muscarinic effect of AF-DX I 16 on atrioventricular nodal conduction with those of pimzepine and atropine as antibradyarrhythmic drugs"Journal of Cardiovascular Phannacology. 33. 912-921 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motomura S: "Differences in vascular selectivity of dihydropyridine calcium antagonists when compared with their effects on respective intracardiac variables"Hirosaki Medical Journal. 51. S156-S163 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohkohchi T, Endoh T, Oikawa K, Seya K, and Satomi S: "Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia"Transplantation. 67. 1173-1177 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K, Furukawa KI, and Motomura S: "A fluorometric assay for cyclic guanosine 3',5'-monophosphate incorporating a Sep-Pak cartridge and enzymatic cycling"Analytical Biochemistry. 272. 243-249 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Daitoku K, Seya K, and Motomura S: "Cilnidipine suppresses DMPP-induced cardiac sympathetic nerve activation in canine blood-perfused papillary muscle"Journal of Cardiovascular Pharmacology. 34(Suppl.4). S81-S84 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki S. Daitoku K, Iwasa A, and Motomura S: "NO is involved in MCh-nduced accentuated antagonism via type 11 PDE in the canine, blood-perfused SA node"American Journal of Physiology. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K, Ohkohchi hl. Shibuya H, Satoh M, Oikawa K, Fukumori T, Satomi S, and Motomura S: "A chemiluminescent assay for hydroperoxide level of phosphatidy]cho]ine hydroperoxide fraction purified by two Sep-Pak cartridges in biological samples"Journal of Pharmaceutical and Biomedical Analysis. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seya K, Daitoku K, and Motomura S: "Norepinephrine measurement in the isolated, blood-perfused papillary muscle of dog using exvivomicrodialysis"Journal of Pharmacological and Toxicologica] Method. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki S. et al.: "Comparison of anti-M2 muscarinic effect of AF-DX116 on atrioventricular nodal conduction with those of pirenzepine and atropine as antibrady arrhythmic drugs"J.Cardiorasc.Pharmacol.. 33. 912-921 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohkohchi N.et al.: "Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia"Transplantation. 67. 1173-1177 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seya K. et al.: "A fluorometric assay for cyclic guanosine 3',5'-monophosphate incorporating a Sep-Pak cartridge and enzymatic cycling"Anal.Biochem.. 272. 243-249 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Daitoku K. et al.: "Cilnidipine suppresses DMPP-induced cardiac sympathetic nerve activation in canine blood-pertused papillary muscle"J.Cardiorasc.Pharmacol.. 34. s81-s84 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seya K. et al.: "A chemiluminescent assay for hydroperoxide level of phosphatidylcholine hydroperoxide fraction purified by two Sep-Pak cartridges in biological samples"J.Pharmaceut. Biomed. Anal.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seya,K.: "Pharmacological properties of pteleprenine,a quinoline alkatad extracted from orira japonica,on guinea-pig sleam and canine leftatrium" J.Pharm.Pharmacol.50(7). 803-807 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sasaki,S.: "Comparison of anti-M_2-Muscarinic effect of AF-DF116 on Atricventriwlar Nodal conduction with those of Pirenzepine and atmoping as Anti- bradyarrhythmicdrugs" J.Cardioras.Pharmacol. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Motomura,S.et al.: "Time course of a urtra-shorting β_1-adrenoceptor blocking drug,ONO-1101" J.Cardiorasc.Pharmacol.31(3). 335-340 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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