TY - JOUR
T1 - In vivo direct monitoring of vagal acetylcholine release to the sinoatrial node
AU - Shimizu, Shuji
AU - Akiyama, Tsuyoshi
AU - Kawada, Toru
AU - Shishido, Toshiaki
AU - Yamazaki, Toji
AU - Kamiya, Atsunori
AU - Mizuno, Masaki
AU - Sano, Shunji
AU - Sugimachi, Masaru
N1 - Funding Information:
This study was supported by Grants-in-Aid for scientific research (No. 19591829 and 20390462) from the Ministry of Education, Culture, Sports, Science and Technology; by Health and Labor Sciences Research Grants (H18-Iryo-Ippan-023, H18-nano-Ippan-003, H19-nano-Ippan-009 and H20-katsudo-Shitei-007) from the Ministry of Health, Labour and Welfare of Japan; and by the Industrial Technology Research Grant Program from New Energy and Industrial Technology Development Organization of Japan.
PY - 2009/6/15
Y1 - 2009/6/15
N2 - To directly monitor vagal acetylcholine (ACh) release into the sinoatrial node, which regulates heart rate, we implanted a microdialysis probe in the right atrium near the sinoatrial node and in the right ventricle of anesthetized rabbits, and perfused with Ringer's solution containing eserine. (1) Electrical stimulation of right or left cervical vagal nerve decreased atrial rate and increased dialysate ACh concentration in the right atrium in a frequency-dependent manner. Compared to left vagal stimulation, right vagal nerve stimulation decreased atrial rate to a greater extent at all frequencies, and increased dialysate ACh concentration to a greater extent at 10 and 20 Hz. However, dialysate ACh concentration in the right atrium correlated well with atrial rate independent of whether electrical stimulation was applied to the right or left vagal nerve (atrial rate = 304 - 131 × log[ACh], R2 = 0.77). (2) Right or left vagal nerve stimulation at 20 Hz decreased atrial rate and increased dialysate ACh concentrations in both the right atrium (right, 17.9 ± 4.0 nM; left, 7.9 ± 1.4 nM) and right ventricle (right, 0.9 ± 0.3 nM; left, 1.0 ± 0.4 nM). However, atrial dialysate ACh concentrations were significantly higher than ventricular concentrations, while ventricular dialysate ACh concentrations were not significantly different between right and left vagal nerve stimulation. (3) The response of ACh release to right and left vagal nerve stimulation was abolished by intravenous administration of a ganglionic blocker, hexamethonium bromide. In conclusion, ACh concentration in dialysate from the right atrium, sampled by microdialysis, is a good marker of ACh release from postganglionic vagal nerves to the sinoatrial node.
AB - To directly monitor vagal acetylcholine (ACh) release into the sinoatrial node, which regulates heart rate, we implanted a microdialysis probe in the right atrium near the sinoatrial node and in the right ventricle of anesthetized rabbits, and perfused with Ringer's solution containing eserine. (1) Electrical stimulation of right or left cervical vagal nerve decreased atrial rate and increased dialysate ACh concentration in the right atrium in a frequency-dependent manner. Compared to left vagal stimulation, right vagal nerve stimulation decreased atrial rate to a greater extent at all frequencies, and increased dialysate ACh concentration to a greater extent at 10 and 20 Hz. However, dialysate ACh concentration in the right atrium correlated well with atrial rate independent of whether electrical stimulation was applied to the right or left vagal nerve (atrial rate = 304 - 131 × log[ACh], R2 = 0.77). (2) Right or left vagal nerve stimulation at 20 Hz decreased atrial rate and increased dialysate ACh concentrations in both the right atrium (right, 17.9 ± 4.0 nM; left, 7.9 ± 1.4 nM) and right ventricle (right, 0.9 ± 0.3 nM; left, 1.0 ± 0.4 nM). However, atrial dialysate ACh concentrations were significantly higher than ventricular concentrations, while ventricular dialysate ACh concentrations were not significantly different between right and left vagal nerve stimulation. (3) The response of ACh release to right and left vagal nerve stimulation was abolished by intravenous administration of a ganglionic blocker, hexamethonium bromide. In conclusion, ACh concentration in dialysate from the right atrium, sampled by microdialysis, is a good marker of ACh release from postganglionic vagal nerves to the sinoatrial node.
KW - Acetylcholine
KW - Anesthetized rabbit
KW - Heart rate
KW - Microdialysis
KW - Right atrium
KW - Sinoatrial node
KW - Vagal nerve activity
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U2 - 10.1016/j.autneu.2009.02.006
DO - 10.1016/j.autneu.2009.02.006
M3 - Article
C2 - 19278905
AN - SCOPUS:67349099111
SN - 1566-0702
VL - 148
SP - 44
EP - 49
JO - Autonomic Neuroscience: Basic and Clinical
JF - Autonomic Neuroscience: Basic and Clinical
IS - 1-2
ER -