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2003 Fiscal Year Final Research Report Summary

Study on the role of the kallikrein-kinin system in the cardiovascular diseases

Research Project

Project/Area Number 13672315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKobe Gakuin University

Principal Investigator

OKAMOTO Hiroshi  Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Professor, 薬学部, 教授 (00028870)

Co-Investigator(Kenkyū-buntansha) TAKANO Masaoki  Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Assistant Professor, 薬学部, 助手 (30258107)
YAYAMA Katsutoshi  Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Associate Professor, 薬学部, 助手 (30248108)
Project Period (FY) 2001 – 2003
Keywordsheart / bradykinin / angiotensin / B2-receptor / angiotensin receptor / cardiac hypertrophy / hypertension / vessel
Research Abstract

Studies have been undertaken to elucidate a role of the kallikrein-kinin system(KKS) in the cardiovascular diseases, such as the cardiac hypertrophy and hypertension. The abdominal aortic banding produced a transient reduction of the bradykinin B2-receptor mRNA in mouse heart before a development of the cardiac hypertrophy. The administration of angiotensin II(Ang II) type 1(AT1) receptor antagonist inhibited the pressure-overload-induced down-regulation of cardiac B2-receptor, suggesting a role of the renin-angiotensin system in regulating B2-receptor expression in cardiac tissue. Tisssue kallikrein was found to be synthesized and secreted by human endothelial cells, suggesting a presence of the local KKS,in vascular endothelium. The abdominal aortic banding produced an up-regulation of the Ang II type 2(AT2) receptor mRNA in pressure-overloaded thoracic aorta in rats and mice, and the administration of AT1-receptor antagonist inhibited the up-regulation of aortic AT2-receptor. The contractile response to Ang II was decreased in pressure-overloaded thoracic aorta in the endothelium-dependent manner, and the decreased response restored to sham-levels by either. AT2-receptor antagonist or B2-receptor antagonist. The aortic banding elicited a marked increase in cGMP content of pressure-overloaded thoracic aortas, and the administration of antagonists for either AT2-or B2-receptor reduced the elevated cGMP contents to sham levels. These results suggest that the aortic banding induced down-regulation of cardiac B2-receptor expression via the activation of AT1-receptor, while the up-regulation of the AT2-receptor in pressure-overloaded aorta through increased circulating Ang II via the AT1-receptor, thereby activating a vasodilatory pathway in vessels through the AT2-receptor via the kinin/cGMP system.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 屋山勝俊, 日吉裕美, 岡本 博: "Expression of bradykinin B2-receptor, kallikrein and kininogen mRNAs in the heart are altered in pressure-overloaded cardiac hypertrophy in mice."Biol.Pharm.Bull.. 24. 34-38 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 屋山勝俊, 松岡哲志, 長岡誠, 島津絵里, 鷹野正興, 岡本 博: "Down-regulation of bradykinin B_2-receptor mRNA in the heart in pressure overload cardiac hypertrophy in the rat."Biochem.Pharmacol.. 65. 1017-1025 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 屋山勝俊, 国松直美, 寺西由美子, 鷹野正興, 岡本 博: "Tissue kallikrein is synthesized and secreted by human vascular endothelial cells."Biochim.Biohys.Acta. 1593. 231-238 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 屋山勝俊, 堀井美幸, 日吉裕美, 鷹野正興, 岡本 博, 籠田智美, 国友 勝: "Up-regulation of angiotensin II type 2 receptor in rat thoracic aorta by pressure-overload."J.Pharmacol.Exp.Ther.. 308. 736-743 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 日吉裕美, 屋山勝俊, 鷹野正興, 岡本 博: "Stimulation of cyclic GMP production via At_2- and B_2-receptors in the pressure-overloaded aorta after banding."Hypertension. In press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岡本 博, 屋山勝俊: "RASとキニンの接点"Angiotensin Research. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsutoshi Yayama: "Expressions of bradykinin B2-receptor, kallikrein, and kininogen mRNAs in the heart are altered in pressure-overload cardiac hypertrophy in mice."Biol.Pharm.Bull.. 24. 34-38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsutoshi Yayama: "Down-regulation of bradykinin B2-receptor mRNA in The heart in pressure-overload cardiac hypertrophy in the rat."Biochem.Pharmacol.. 65. 1017-1025 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsutoshi Yayama: "Tissue kallikrein is synthesized and secreted by human vascular endothelial cells."Biochim.Biophys.Acta. 1593. 231-238 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsutoshi Yayama: "Up-regulation of angitoensin II type 2 receptor in rat thoracic aorta by pressure-overload."J.Pharmacol.ExTher.. 308. 736-743 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiromi Hiyoshi: "Stimulation of cyclic GMP production via AT2-and B2-receptors in the pressure-overloaded aorta after banding."Hypertension. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroshi Okamoto: "Cross-talk between the rerun-angiotensin and kallikrein-kinin systems in vascular tissues."J.Angiotensin Res.(Review article in Japanese). (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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