Presynaptic modulation of heart rate responses to cardiac nerve stimulation in pithed rats

The effects of presynaptic alpha-adrenoceptor blockade with phentolamine, before and after inhibition of uptake-1 with cocaine, on the positive chronotropic response to cardiac sympathetic nerve stimulation in pithed rats was investigated. Phentolamine or cocaine each enhanced the cardiac responses to stimulation at 1 Hz for 15 sec by 10-25%; the combination of the drugs caused no greater enhancement than did either drug alone. Cocaine considerably potentiated the tachycardia produced during prolonged stimulation at 0.1 but not at 0.2-1 Hz. Phentolamine potentiated the responses to stimulation at 0.2 and 0.5 Hz by 21 and 12%, respectively, but not those at 0.1 or 1 Hz. After cocaine, phentolamine caused a further small increase in the response at 0.1 Hz but not other frequency. It is concluded that presynaptic alpha-adrenoceptors exert only modest control over the responses of the rat heart to cardiac nerve stimulation and that this modulation is little influenced by uptake-1.