Contrasting Effects of Clonidine and 5-Hydroxytryptophan on Spinal Sympathetic Pathways

Abstract

The effects of clonidine HCI were compared with those of 5-HTP on transmission through two spinal sympathetic pathways, segmental spinal reflex pathways and descending intraspinal excitatory pathways, in unanesthetized spinal cats. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine (5–50 ug/kg) produced a parallel, dose-dependent depression of transmission through each pathway. The intraspinal pathway was five times more sensitive than the spinal reflex pathway (ED50's, 6 and 30 ug/kg), and the spinal reflex pathway could not be depressed by more than 60% even by higher doses. In contrast, 5-HTP was more effective in depressing the spinal reflex than the intraspinal pathway (ED50's, 32 and 44 mg/kg), and both pathways could be depressed completely. Small doses of tolazoline or yohimbine rapidly antagonized the effects of clonidine but not 5-HTP. Clonidine and 5-HTP appear to depress the excitability of sympathetic preganglionic neurons by activating alpha₂- and 5-HT receptors, respectively. Each mechanism may contribute independently to regulation of the sympathetic outflow.