Interactions between clonidine and alpha-adrenoceptor blocking drugs on the tachycardic response to stimulation of the cardiac nerve in dogs

In pentobarbital-treated dogs clonidine (10 micrograms/kg) reduced the increase in heart rate caused by electrical stimulation of the cardiac nerve (1-10 Hz). We studied the actions of six alpha-adrenoceptor blocking drugs. Yohimbine (0.3 mg/kg) and phentolamine (1 mg/kg) potentiated the effects of nerve stimulation and antagonized the inhibitory effects of clonidine. Piperoxan (1 mg/kg) increased the response to nerve stimulation but antagonized the effects of clonidine only at the lowest frequency of stimulation. Thymoxamine (1 mg/kg) and prazosin at high doses (1 mg/kg) also antagonized the effects of clonidine but failed to increase the positive chronotropic response to stimulation of the cardiac nerve. AR-C239, a new and potent alpha-adrenoceptor blocking agent, changed neither the response to nerve stimulation nor the inhibitory effect of clonidine. The effects of all these drugs were observed at doses which reduced or reversed the pressor response to adrenaline. Therefore, our results afford further evidence for a dissimilarity between postsynaptic and presynaptic alpha-adrenoceptors in the dog. In addition, they show that the failure of an alpha-adrenoceptor blocking compound to increase the response to nerve stimulation does not necessarily indicate a lack of presynaptic alpha-adrenoceptor blockade.