THE EFFECT OF CLONIDINE ON ADRENERGIC NERVE FUNCTION IN VAGOTOMIZED AND NONVAGOTOMIZED ANIMALS

¹ Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit, New Jersey

The effect of clonidine (15 and 30µg/kg i.v.) on responses to adrenergic nerve stimulation and pressor substances was studied in vagotomized and nonvagotomized dogs. The Positive chronotropic responses. but not the associated rise in blood pressure, to right postganglionsic cardioaccelerator nerve stimulation in nonvagotomized dogs were inhibited by clonidine. However, clonidine had no effect on the positive chronotropic responses to either pre- or postganglionic cardioaccelerator nerve stimulation in vagotomized or atropine-treated dogs. These results suggest that an apparent inhibition of responses to cardioaccelerator nerve stimulation by clonidine, in dogs with normal vagal innervation, may be due to enhancement of baroreceptor reflexes wihich are triggered by an elevation of blood pressure which accompanies nerve stimulation. Clonidine inhibited pressor and positive chronotropic effects of McN A-343, a muscarinic ganglion stimulant, but not of 1,1-dimethyl-4-phenylpiperazinium iodide, a nicotinic ganglion stimulant, in both vagotomized and nonvagotomized dogs, which suggests that clonidine may cause specific inhibition of muscarinic ganglionic receptors.