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2003 Fiscal Year Final Research Report Summary

EFFERENT MECHANISMS OF DEFENSE RESPONSE FROM THE HYPOTHALAMUS

Research Project

Project/Area Number 14570037
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

KUWAKI Tomoyuki  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80205260)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Akira  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT, 大学院・医学研究院, 助手 (40343090)
FUKUDA Yasuichiro  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (10009649)
Project Period (FY) 2002 – 2003
KeywordsHYPOTHALAMUS / DEFENSE RESPONSE / OREXIN / STRESS / KNOCKOUT MICE / SYMPATHETIC NERVOUS SYSTEM / USA / INTERNATIONAL INFORMATION EXCHANGE
Research Abstract

The perifornical area of the hypothalamus has been known as the center for defense response, or "fight or flight" response, which is characterized by concomitant rise in arterial blood pressure (AP), heart rate (HR), and respiratory frequency (Rf). We examined whether orexin, a recently identified hypothalamic neuropeptide, contributes to the defense response and basal cardiovascular regulation using orexin knockout mice. Microinjection of a GABA-A receptor antagonist, bicuculline methiodide, to the perifornical area in urethane-anesthetized wild-type mice elicited dose-dependent increases in AP, HR, and Rf. Although similar changes were observed in orexin knockout mice, intensities were smaller and duration was shorter than those in wild-type mice.Moreover, in an awake and freely moving condition, telemeter-indwelling orexin knockout mice showed diminished cardiovascular and behavioral responses to emotional stress in the resident-intruder test. We also found that basal AP in orexin knockout mice was significantly lower by 〜20 mmHg in both anesthetized and awake conditions. Alpha-adrenergic blockade with prazosin or ganglion blockade with hexamethonium cancelled the difference in basal AP. HR and cardiac contractile parameters by echocardiography did not differ between the two strains of mice. These results indicate lower sympathetic vasoconstrictor tone in knockout mice. The present study suggests that orexin-containing neurons in the perifornical area play a crucial role as one of the efferent pathways of defense response and also operate as a regulator of AP at basal condition by activating sympathetic outflow.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] T.Kuwaki: "Role of orexin in defense response and regulation of basal blood pressure."Experimental Neurobiology. 11. 73 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kayaba: "Role of orexin as an efferent transmitter of defense reaction."Japanese Journal of Physiology. 52. S81 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kayaba: "Involvement of orexin as a modulator of defense reaction and blood pressure."Neuroscience Research. Suppl.26. S121 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kayaba: "Attenuated defense response and low basal blood pressure in orexin knockout mice."American Journal of Physiology : Regulatory, Integrative & Comparative Physiology. 285. R581-R593 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑木共之: "ストレス防衛反応時の自律神経出力調節におけるオレキシンの役割"日本自律神経学会雑誌. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kayaba: "Involvement of orexin in defense response and cardiovascular regulation."Japanese Journal of Physiology. 53. S268 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki: "Hypotension and attenuated defense response in orexin knockout mice."Neuroscience Research. 46. S39 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki, et al.: "Role of orexin in defense response and regulation of basal blood pressure."Exp.Neurobiol.. 11(2). 73 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kayaba, et al.: "Role of orexin as an efferent transmitter of defense reaction."Jpn J Physiol.. 52. S81 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kayaba, et al.: "Involvement of orexin as a modulator of defense reaction and blood pressure"Neurosci Res. suppl 26. S121 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kayaba, et al.: "Attenuated defense response and low basal blood pressure in orexin knockout mice."Am.J.Physiol Regul Integ Comp Physiol. 285(3). R581-R593 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kuwaki, et al.: "Hypotension and attenuated defense response in orexin knockout mice."Neurosci Res. 46. S39 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kayaba, et al.: "Involvement of orexin in defense response and cardiovascular regulation."Jpn J Physiol. 53. S268 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kuwaki: "Role of orexin in the regulation of autonomic outflow during defense response against stress."The Autonomic Nervous System. (in press).

    • 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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