Add time:09/26/2019         Source:sciencedirect.com

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misuet al. (1995)Adv. Pharmac.32, 427–459]. L-DOPA as a probable neurotransmitter for the primary baroreceptor afferents tonically functions to mediate cardiodepressor control in the nucleus tractus solitarii and also tonically functions to mediate cardiopressor control in the rostral ventrolateral medulla of rats. We further attempted to clarify whether a transmitter-like L-DOPA system is altered in these areas of adult spontaneously hypertensive rats. By microdialysis in the left nucleus tractus solitarii area, the basal L-DOPA release was lower in spontaneously hypertensive rats than that in Wistar-Kyoto rats. This release was partially reduced by tetradotoxin (1 μM) to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is impaired in this nucleus of spontaneously hypertensive rats. This impairment is not secondarily due to decrease in formation or increase in decar☐ylation of L-DOPA, since tyrosine hydroxylase activity was increased in spontaneously hypertensive rats, compared to Wistar-Kyoto rats, while no difference of L-aromatic amino acid decar☐ylase activity was seen in the caudal dorsomedial 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 that that of Wistar-Kyoto rats. On the other hand, in the left rostral ventrolateral medulla, the basal L-DOPA release was higher in spontaneously hypertensive rats that in Wistar-Kyoto rats. This release was also partially reduced by tetrodotoxin to the same absolute levels in the two strains. Tonic neuronal L-DOPA release is enhanced in spontaneously hypertensive rats. This enhancement seems to include partially a decrease in decar☐ylation of L-DOPA, since L-aromatic amino acid decar☐ylase 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 tachycardia. Importantly, a pressor response of spontaneously hypertensive rats to L-DOPA at lower doses was slightly greater than that of Wistar-Kyoto rats.L-DOPA seems to play a transmitter-like role in blood pressure regulation at levels of the nucleus tractus solitarii and rostral ventrolateral medulla in rats. Impaired tonic neuronal activity to release L-DOPA in the nucleus tractus solitarii, enhanced tonic neuronal activity including a decrease in decar☐ylation and an increase in sensitivity of a recognition site for L-DOPA in the rostral ventrolateral medulla may be involved in the maintenance of hypertension in spontaneously hypertensive rats.

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