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2014 Fiscal Year Research-status Report

Chronic electrical activation of the arterial baroreflex in hypertensive rats - determining the role of unmyelinated baroreceptors

Research Project

Project/Area Number 26750153
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TURNER MICHAEL  独立行政法人国立循環器病研究センター, 研究所, 流動研究員 (90714204)

Project Period (FY) 2014-04-01 – 2016-03-31
Keywordsbaroreflex / hypertension / resiniferatoxin / capsaicin / nerve stimulation
Outline of Annual Research Achievements

Baroreflex activation therapy (BAT) uses electrical stimulation of baroreceptors to reduce arterial pressure (AP) in resistant hypertensive patients. However, the electrical stimulation of the two types of baroreceptor afferents, myelinated (A-fiber) and unmyelinated (C-fiber), may have significantly different outcomes. We hypothesize that the central processing of A-fiber and C-fiber baroreceptors are affected differently during the development of hypertension and during stimulation in BAT. To understand the role of C-fiber baroreceptor pathway, a stimulation electrode for the left aortic depressor nerve (ADN) was implanted in rats, and the effect of ADN stimulation was chronically monitored. After confirming the stimulation-induced hypotensive response, resiniferatoxin was administered intraperitoneally to block C-fibers. The successful blockade of C-fiber afferents was confirmed by the absence of blinking response to eye drop of a small amount of capsaicin. The blockade of systemic C-fiber afferents was expected to elevate AP in normotensive rats, however, AP did not increase after the administration of resiniferatoxin. It was speculated that the TRPV1 receptors participate in drinking behavior, and resiniferatoxin may have caused dehydration of animals due to the loss of thirst. In acute experiments, we have confirmed that the C-fiber afferents are important for baroreflex-mediated sustained AP regulation, and the function of C-fiber afferents is impaired in spontaneously hypertensive rats. Therefore, we are planning to perform chronic ADN stimulation in SHR next year.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Chronic implantation of the stimulation electrode for the aortic depressor nerve, and the blockade of C-fiber afferents by intraperitoneal administration of resiniferatoxin were successful. However, the blockade of C-fiber afferents did not chronically elevate arterial pressure in normotensive rats. Meanwhile, we performed an acute baroreflex study to compare the function of A- and C-fiber afferents in normotensive rats and spontaneously hypertensive rats.

Strategy for Future Research Activity

As described in the progress status, because resiniferatoxin did not increase arterial pressure in normotensive rats, we are now planning to implant the stimulation electrode in spontaneously hypertensive rats and examine the baroreflex responses. Other models of hypertension such as Dahl salt sensitive rats will be examined for the relative roles of A- and C-fiber baroreceptors.

Causes of Carryover

少額であるので、次年度に必要な物品と合わせて支出する。

Expenditure Plan for Carryover Budget

少額であるので、次年度に必要な物品と合わせて支出する。

  • Research Products

    (8 results)

All 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Effects of tempol on baroreflex neural arc versus peripheral arc in normotensive and spontaneously hypertensive rats2015

    • Author(s)
      Kawada T, Sata Y, Shimizu S, Turner MJ, Fukumitsu M, Sugimachi M
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol

      Volume: 未定 Pages: 未定

    • DOI

      10.1152/ajpregu.00525.2014

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Calibration of baroreflex equilibrium diagram based on exogenous pressor agents in chronic heart failure rats2015

    • Author(s)
      Kawada T, Li M, Sata Y, Zheng C, Turner MJ, Shimizu S, Sugimachi M
    • Journal Title

      Clin Med Insights Cardiol

      Volume: 9(Suppl 1) Pages: 1-9

    • DOI

      10.4137/CMC.S18759.

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acute effects of arterial baroreflex on sympathetic nerve activity and plasma norepinephrine concentration2014

    • Author(s)
      Kawada T, Akiyama T, Shimizu S, Sata Y, Turner MJ, Shirai M, Sugimachi M
    • Journal Title

      Auton Neurosci

      Volume: 186 Pages: 62-68

    • DOI

      10.1016/j.autneu.2014.10.016

    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 高血圧自然発症ラットにおける動脈圧反射中枢弓の動特性2014

    • Author(s)
      川田 徹, ターナー マイケル, 杉町 勝
    • Organizer
      第50回高血圧関連疾患モデル学会学術総会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-12-05 – 2014-12-06
  • [Presentation] 左心低形成症候群に対するハイブリッド手術の血行動態シミュレーション2014

    • Author(s)
      清水秀二, 川田 徹, マイケル J ターナー, 宍戸稔聡, 杉町 勝
    • Organizer
      第107回近畿生理学談話会
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-25 – 2014-10-25
  • [Presentation] Dynamic carotid baroreflex characteristics are unaffected by the electrical stimulation of aortic baroreceptors2014

    • Author(s)
      Turner MJ, Shimizu S, Kawada T, Sugimachi M
    • Organizer
      第107回近畿生理学談話会
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-25 – 2014-10-25
  • [Presentation] Static characteristics of the aortic baroreflex following blockade of unmyelinated baroreceptor activity with resiniferatoxin2014

    • Author(s)
      Turner MJ, Kawada T, Sugimachi M
    • Organizer
      Life Engineering Symposium 2014
    • Place of Presentation
      金沢
    • Year and Date
      2014-09-17 – 2014-09-19
  • [Presentation] 交感神経活動と血中ノルアドレナリンの関係は直線的か?2014

    • Author(s)
      川田 徹, 清水秀二, 李 梅花, ターナー マイケル, 秋山 剛, 杉町 勝
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      博多
    • Year and Date
      2014-07-04 – 2014-07-05

URL: 

Published: 2016-06-01  

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