ALTERED TONIC L-3,4-DIHYDROXYPHENYLALANINE SYSTEMS IN THE NUCLEUS-TRACTUS-SOLITARII AND THE ROSTRAL VENTROLATERAL MEDULLA OF SPONTANEOUSLY HYPERTENSIVE RATS

We have proposed that L-3,4-dihydroxyphenylalanine (L-DPPA) is a neuro transmitter in the central nervous system [Y. Misu et al. (1995) Adv. Pharmac. 32, 427-459]. L-DOPA as a probable neurotransmitter for the p rimary baroreceptor afferents tonically functions to mediate cardiodep ressor control in the nucleus tractus solitarii and also tonically fun ctions to mediate cardiopressor control in the rostral ventrolateral m edulla of rats. We further attempted tb clarify whether a transmitter- like L-DOPA system is altered in these areas of adult spontaneously hy pertensive rats. By microdialysis in the left nucleus tractus solitari i area, the basal L-DOPA release was lower in spontaneously hypertensi ve rats than that in Wistar-Kyoto rats. This release was partially red uced by tetrodotoxin (1 mu M) to the same absolute levels in the two s trains. Tonic neuronal L-DOPA release is impaired in this nucleus of s pontaneously hypertensive rats. This impairment is not secondarily due to decrease in formation or increase in decarboxylation oft DOPA, sin ce tyrosine hydroxylase activity was increased in spontaneously hypert ensive rats, compared to Wistar-Kyoto rats, while no difference of L-a romatic amino acid decarboxylase activity was seen in the caudal dorso medial medulla including the nucleus. L-DOPA (10-300 ng) microinjected into the nucleus produced dose-dependent hypotension and bradycardia. A maximum depressor response of spontaneously hypertensive rats to L- DOPA at higher doses was slightly greater than that of Wistar-Kyoto ra ts. On the other hand, in the left rostral ventrolateral medulla, the basal L-DOPA release was higher in spontaneously hypertensive rats tha n that in Wistar-Kyoto rats. This release was also partially reduced b y tetrodotoxin to the same absolute levels in the two strains. Tonic n euronal L-DOPA release is enhanced in spontaneously hypertensive rats. This enhancement seems to include partially a decrease in decarboxyla tion of L-DOPA, since L-aromatic amino acid decarboxylase activity was decreased in spontaneously hypertensive rats compared to Wistar-Kyoto rats, while no difference in tyrosine hydroxylase activity was seen. L-DOPA (10-600 ng) produced dose-dependent hypertension and tachycardi a. Importantly, a presser response of spontaneously hypertensive rats to L-DOPA at lower doses was slightly greater than that of Wistar-Kyot o rats. L-DOPA seems to play a transmitter-like role in blood pressure regulation at levels of the nucleus tractus solitarii and rostral ven trolateral medulla in rats. Impaired tonic neuronal activity to releas e L-DOPA in the nucleus tractus solitarii, enhanced tonic neuronal act ivity including a decrease in decarboxylation and an increase in sensi tivity of a recognition site for L-DOPA in the rostral ventrolateral m edulla may be involved in the maintenance of hypertension in spontaneo usly hypertensive rats.