An L-DOPAergic relay from the posterior hypothalamic nucleus to the rostral ventrolateral medulla and its cardiovascular function in anesthetized rats

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotrans mitter in the central nervous system [Misu Y. et al. (1996) Frog. Neurobiol . 49, 415-454]. Herein, we attempt to clarify whether lesions in the poster ior hypothalamic nucleus decrease the tissue content of L-DOPA in the rostr al ventrolateral medulla. We also attempt to clarify whether or not endogen ous L-DOPA is evoked by electrical stimulation of the posterior hypothalami c nucleus. It is possible that evoked L-DOPA functions as a transmitter can didate to activate presser sites of the rostral ventrolateral medulla in an esthetized rats. Electrolytic lesions were made in the bilateral posterior hypothalamic nucleus by a monopolar direct current of 2 mA for 10 s, 10 day s before measurements. The effect of the lesions was to selectively decreas e the tissue content of L-DOPA by one-half in the right rostral ventrolater al medulla. Decreases in the amounts of dopamine, noradrenaline or adrenali ne were not observed. Decreases were also not evident in the right caudal v entrolateral medulla. During microdialysis of the right rostral ventrolater al medulla, extracellular basal levels of L-DOPA and three types of catecho lamine were consistently detectable by high-performance liquid chromatograp hy with electrochemical detection. Tetrodotoxin (1 mu M) perfused into the right rostral ventrolateral medulla gradually decreased basal levels of L-D OPA by 25%; it decreased basal levels of noradrenaline and adrenaline by 25 -30% and dopamine levels by 40%. Intensive electrical stimulation of the ip silateral posterior hypothalamic nucleus (50 Hz, 0.3 mA, 0.1 ms duration, t wice for 5 min at an interval of 5 min) selectively caused the release of L -DOPA in a repetitive and constant manner. The stimulation was accompanied by hypertension and tachycardia. However, catecholamines were not released. Tetrodotoxin suppressed the release of L-DOPA, but partially inhibited hyp ertension with only a slight inhibition of tachycardia evoked by stimulatio n of the posterior hypothalamic nucleus. L-DOPA methyl ester, a competitive L-DOPA antagonist, was bilaterally microinjected into presser sites of the rostral ventrolateral medulla at 1.5 mu g x 2 and 3 mu g x 2. The antagoni st dose-dependently and consistently antagonized presser and tachycardiac r esponses to mild transient stimulation of the unilateral posterior hypothal amic nucleus (33 Hz, 0.2 mA, 0.1 ms duration, for 10 s). In addition, the a ntagonist alone (3 mu g x 2) elicited hypotension and bradycardia. These results show that an L-DOPAergic relay may project from the posterior hypothalamic nucleus directly to presser sites of the rostral ventrolatera l medulla and/or indirectly to certain neurons near presser sites in microc ircuits of the same region. When released, L-DOPA appears to function tonic ally to activate presser sites; it also appears to be involved in the maint enance and regulation of blood pressure and heart rate. (C) 1999 IBRO. Publ ished by Elsevier Science Ltd.