Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog heart.
There is no data about whether botulinum neurotoxin inhibits the parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. Therefore, we investigated whether botulinum toxin (type A) injected into the sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation of the preganglionic parasympathetic nerves in the heart of the anesthetized dog. Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation) prolonged the atrial interval but not the atrioventricular (AV) interval, and cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV intervals. After botulinum toxin (20 or 25 mouse units) was injected into the SA fat pad, it gradually inhibited the prolongation of the atrial interval evoked by SAP and CV stimulations but not the prolongation of the AV interval evoked by CV stimulation. Conditioning successive stimulation of the cervical vagus nerves accelerated the inhibition by botulinum toxin of the chronotropic response to CV stimulation. These results indicate that selective injection of botulinum toxin into the SA fat pad blocks bradycardia mediated by parasympathetic ganglionic activation in the dog heart.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Masato
M
Tsuboi
Yasuyuki
Y
Furukawa
Fumio
F
Kurogouchi
Koichi
K
Nakajima
Masamichi
M
Hirose
Shigetoshi
S
Chiba
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D004285:Dogs; D005726:Ganglia, Parasympathetic / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D019274:Botulinum Toxins, Type A