Parasympatholytic effects of vecuronium are mediated by nicotinic and muscarinic receptors in hearts of anesthetized dogs.
We investigated the blocking effects of vecuronium and pancuronium on the negative chronotropic and dromotropic responses to stimulation of the parasympathetic nerves in the anesthetized, open-chest dog. We stimulated the intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) or to the atrioventricular nodal region (AVP stimulation). SAP stimulation or AVP stimulation selectively decreased heart rate or increased atrioventricular conduction time, respectively. Vecuronium and pancuronium inhibited the chronotropic response to SAP stimulation and the dromotropic response to AVP stimulation in a dose-dependent manner. The ID50 of each drug for the dromotropic response was less than that for the chronotropic response. The blocking effect of vecuronium on the negative cardiac responses to parasympathetic stimulation was about 10-fold less potent than that of pancuronium. These results suggest that the blocking effects of vecuronium and pancuronium on the negative chronotropic and dromotropic responses to parasympathetic stimulation differ from those of atropine in the heart. In the isolated right atrium perfused with blood from the support dog, vecuronium, injected into the external jugular vein of the support dog, dose-dependently inhibited the negative chronotropic and inotropic responses to carbachol or SAP stimulation and the negative followed by positive chronotropic and inotropic responses to nicotine. The ID50 values for carbachol, nicotine and SAP stimulation were not significantly different. These results suggest that parasympatholytic effects of vecuronium are mediated by not only muscarinic receptors but also neuronal nicotinic receptors in hearts of anesthetized dogs.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
M
M
Narita
Y
Y
Furukawa
M
M
Murakami
M
M
Takei
L M
LM
Ren
S
S
Chiba
D000758:Anesthesia; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010197:Pancuronium / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014673:Vecuronium Bromide / Q000494:pharmacology*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014673:Vecuronium Bromide; D010197:Pancuronium