L-DOPA systems for blood pressure regulation in the lower brainstem

Abstract

We have explored probable neurotransmitter roles of l-3,4-dihydroxyphenylalanine ( l-DOPA) in baroreceptor reflex and blood pressure regulation in depressor sites of the nucleus tractus solitarii (NTS) and the caudal ventrolateral medulla (CVLM), and in pressor sites of the rostral ventrolateral medulla (RVLM) in anesthetized rats. During microdialysis of these three areas, the basal l-DOPA release is in part tetrodotoxin (TTX)-sensitive and Ca 2+-dependent, high K + Ca 2+-dependently releases l-DOPA. l-DOPA microinjected (10–300 ng) dose-dependently produces postsynaptic depressor responses in the NTS and CVLM and pressor responses in the RVLM, and a recognition site for l-DOPA functions tonically to activate depressor neurons in the NTS and CVLM and pressor neurons in the RVLM. It is highly probable that l-DOPA is a neurotransmitter of the baroreceptor afferents terminating in the NTS, which is based on further findings such as (1) antagonism by a competitive l-DOPA antagonist against depressor responses to aortic nerve stimulation, (2) TTX-sensitive l-DOPA release by aortic nerve stimulation, (3) abolition of baroreceptor-stimulated l-DOPA release by bilateral sino-aortic denervation and (4) decreases in tyrosine hydroxylase (TH)- and l-DOPA-immunoreactivities without modifications of dopamine- and DBH-immunoreactivities in the left NTS and ganglion nodosum 7 days after ipsilateral aortic nerve denervation peripheral to the ganglion. In the NTS, GABA tonically functions to inhibit via GABA A receptors l-DOPA release and depressor responses to l-DOPA, whereas l-DOPA induces GABA release. Impaired TTX-sensitive neuronal activity to release l-DOPA in the NTS and enhanced TTX-sensitive neuronal activity including a decrease in decarboxylation of l-DOPA to dopamine and an increase in sensitivity of the recognition site to l-DOPA in the RVLM are relevant to the maintenance of hypertension in spontaneously hypertensive rats. Decreases in the contents of l-DOPA in the right CVLM 10 days after electrical lesion of the ipsilateral NTS suggest a ‘ l-DOPAergic’ and monosynaptic relay from the NTS to the CVLM. l-DOPA seems to play major roles as a neurotransmitter for baroreceptor reflex and blood pressure regulation in the lower brainstem of rats.