Direct effects of cholinergic stimulation on ventricular automaticity in guinea pig myocardium.
The purpose of these experiments was to determine whether muscarinic cholinergic agonists exerted a negative chronotropic effect in the absence of endogenous norepinephrine in isolated guinea pig ventricular myocardial strips. The chronotropic response to physostigmine (10(-6) M) in control, reserpine-pretreated animals, and in the presence of increased norepinephrine release induced by superfusion of tyramine (10(-5) M), was studied. The control rates in the control, reserpine-pretreated, and tyramine-treated groups were 106 +/- 40, 93 +/- 31, 109 +/- 28/min, respectively. Propranolol (10(-6) M) produced a 23% slowing in rate in control animals and an 8% slowing in reserpine pretreated animals (P less than 0.01), suggesting basal secretion of norepinephrine. Tyramine (10(-5) M) produced a 28% increase in rate in control animals (P less than 0.05) and tyramine (10(-4) M) produced no increase in reserpine-pretreated animals. Physostigmine produced similar negative chronotropic response in control, reserpine-pretreated, and tyramine-treated groups of 45, 49, and 28%, respectively. Physostigmine produced no change in measured Purkinje fiber action potential characteristics, except for a decreased rate of spontaneous diastolic depolarization. Our results demonstrate that physostigmine slows the spontaneous rate in control, reserpine-pretreated and tyramine-treated groups, indicating that muscarinic cholinergic agonists exert a direct negative chronotropic effect at postjunctional cell surface receptors, independent of the presence or level of adrenergic tone.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D010277:Parasympathomimetics; D001285:Atropine; D010830:Physostigmine; D011433:Propranolol; D009638:Norepinephrine; D014439:Tyramine