Functional participation in M1 receptor subtype on chronotropic and dromotropic responses to vagus stimulation in anesthetized dogs.
We investigated blocking effects of pirenzepine, AF-DX 116 and atropine on the negative chronotropic and dromotropic responses to stimulation of the intracardiac vagus nerves in the anesthetized, open-chest dogs. Stimulation of the intracardiac vagus nerves to the sinoatrial nodal region (stimulation of the intracardiac parasympathetic nerves to the sinoatrial nodal region) or to the atrioventricular nodal region (stimulation of intracardiac nerves to the atriventricular region) selectively decreased heart rate or increased atrioventricular conduction time, respectively. Pirenzepine at lower doses (0.3-3 microgram/kg i.v.) attenuated the stimulation of the negative chronotropic response to the intracardiac parasympathetic nerves to the sinoatrial nodal region to 80% of the control response significantly but did not affect the negative dromotropic one. Similarly, higher doses (10-1000 micrograms/kg i.v.) of pirenzepine inhibited the chronotropic and dromotropic responses to each stimulation in a dose-dependent manner. AF-DX 116 (0.3-300 microgram/kg i.v.) inhibited the chronotropic and dromotropic responses to each stimulation in a similar dose-dependent manner. Atropine (1-30 microgram/kg i.v.) blocked the cardiac responses to each stimulation. However, the ID50 of atropine for the chronotropic response was less than that for the dromotropic one, although ID50s of pirenzepine and AF-DX 116 for the chronotropic and dromotropic responses were not different.(ABSTRACT TRUNCATED AT 250 WORDS)
Narita
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Takei
M
M
Murakami
M
M
Ren
L M
LM
Karasawa
Y
Y
Chiba
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; C048593:otenzepad