BARORECEPTOR-AORTIC NERVE-MEDIATED RELEASE OF ENDOGENOUS L-3,4-DIHYDROXYPHENYLALANINE AND ITS TONIC DEPRESSOR FUNCTION IN THE NUCLEUS-TRACTUS-SOLITARII OF RATS

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neuro transmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or not endogenous L-DOPA, as a neurotransmit ter candidate of the primary baroreceptor afferents, tonically functio ns to activate depressor neurons in the nucleus tractus solitarii of a nesthetized rats. By parallel microdialysis in bilateral nucleus tract us solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 mu M) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine hydro xylase inhibitor. Forty to 100 mM K+ concentration-dependently release d L-DOPA. Fifty millimoles K+ repetitively and constantly released L-D OPA. This release was Ca2+-dependent. Stimulation of the left aortic n erve (100 Hz, 8 V) repetitively and constantly released L-DOPA and thi s release was tetrodotoxin-sensitive. Phenylephrine i.v. infused produ ced L-DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bra dycardia were abolished by denervation of the bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a competitive L-D OPA antagonist, when microinjected into depressor sites of the left nu cleus tractus solitarii, antagonized depressor responses to mild stimu lation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist a lone, microinjected bilaterally, elicited a dose-dependent hypertensio n, which was abolished by alpha-methyl-p-tyrosine. Furthermore, by imm unocytochemical analysis seven days after denervation of the left aort ic nerve, tyrosine hydroxylase- and L-DOPA-, but not dopamine- and dop amine-beta-hydroxylase-immunoreactivities decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus nucleus complex area . In the left ganglion nodosum, denervation decreased staining and num ber of L-DOPA-immunoreactive cells and staining of tyrosine hydroxylas e-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that L-DOPA its elf is stereoselectively responsible for cardiovascular control in thi s nucleus, it is probable that L-DOPA is a neurotransmitter of the pri mary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including dep ressor neurons of the nucleus tractus solitarii. Endogenously released L-DOPA itself tonically functions to activate depressor neurons for r egulation of blood pressure in the rat nucleus tractus solitarii.