title: Contrasting effects of presynaptic alpha2-adrenergic autoinhibition and pharmacologic augmentation of presynaptic inhibition on sympathetic heart rate control.
abstract: Presynaptic alpha2-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 alpha2-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 alpha2-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.
authors.affiliation: Department of Physical Therapy, Faculty of Health Sciences, Morinomiya University of Medical Sciences, Osaka 559-8611, Japan. miyamoto@morinomiya-u.ac.jp
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagiya
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi