Leung_1983_J.Pharmacol.Methods_9_117

A simple technique is described for evaluating the effects of drugs on postganglionic cholinergic nerve stimulation in guinea pig atrial tissue. Raising the voltage of stimulation tenfold (high voltage stimulation, HVS) in the left atrium produced a positive inotropic response. Propranolol abolished this effect but failed to reveal a negative inotropic response. However, in atria obtained from 6-hydroxydopamine (6-OHDA) pretreated animals, HVS produced a negative inotropic effect. The magnitude of the response was frequency-dependent and was potentiated by the anticholinesterase dyflos. Tetrodotoxin abolished the response but mecamylamine had no significant effect. Drugs which inhibit cardiac muscarinic receptors caused a parallel shift of the frequency-response relationship. In the right atrium, HVS caused a biphasic inotropic response. Propranolol or 6-OHDA pretreatment inhibited the positive inotropic effect, thereby enhancing the negative inotropic response. The effect did not show as great a dependence on the frequency of stimulation as in the left atrium and was less useful for comparing the effectiveness of muscarinic receptor antagonists.