Contrasting effects of presynaptic α2-adrenergic autoinhibition and pharmacologic augmentation of presynaptic inhibition on sympathetic heart rate control

Tadayoshi Miyamoto, Toru Kawada, Yusuke Yanagiya, Tsuyoshi Akiyama, Atsunori Kamiya, Masaki Mizuno, Hiroshi Takaki, Kenji Sunagawa, Masaru Sugimachi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Presynaptic α2-adrenergic receptors are known to exert feedback inhibition on norepinephrine release from the sympathetic nerve terminals. To elucidate the dynamic characteristics of the inhibition, we stimulated the right cardiac sympathetic nerve according to a binary white noise signal while measuring heart rate (HR) in anesthetized rabbits (n = 6). We estimated the transfer function from cardiac sympathetic nerve stimulation to HR and the corresponding step response of HR, with and without the blockade of presynaptic inhibition by yohimbine (1 mg/kg followed by 0.1 mg·kg -1·h-1 iv). We also examined the effect of the α2-adrenergic receptor agonist clonidine (0.3 and 1.5 mg kg-1·h-1 iv) in different rabbits (n = 5). Yohimbine increased the maximum step response (from 7.2 ± 0.8 to 12.2 ± 1.7 beats/min, means ± SE, P < 0.05) without significantly affecting the initial slope (0.93 ± 0.23 vs. 0.94 ± 0.22 beats min-1·s-1). Higher dose but not lower dose clonidine significantly decreased the maximum step response (from 6.3 ± 0.8 to 6.8 ± 1.0 and 2.8 ± 0.5 beats/min, P < 0.05) and also reduced the initial slope (from 0.56 ± 0.07 to 0.51 ± 0.04 and 0.22 ± 0.06 beats·min-1·s-1, P < 0.05). Our findings indicate that presynaptic α2-adrenergic autoinhibition limits the maximum response without significantly compromising the rapidity of effector response. In contrast, pharmacologic augmentation of the presynaptic inhibition not only attenuates the maximum response but also results in a sluggish effector response.

Original languageEnglish
Pages (from-to)H1855-H1866
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number5
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Rabbits
  • Systems analysis
  • Transfer function
  • α-adrenergic blockade

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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