Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misu et 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 tetrodotoxin (1 microM) 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 decarboxylation 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 decarboxylase 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 than 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 than 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 decarboxylation 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 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.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered tonic L-3,4-dihydroxyphenylalanine systems in the nucleus tractus solitarii and the rostral ventrolateral medulla of spontaneously hypertensive rats. 747 14

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter 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 neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released L-DOPA. Fifty millimoles K+ repetitively and constantly released L-DOPA. This release was Ca(2+)-dependent. Stimulation of the left aortic nerve (100 Hz, 8 V) repetitively and constantly released L-DOPA and this release was tetrodotoxin-sensitive. Phenylephrine i.v. infused produced L-DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bradycardia were abolished by denervation of the bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a competitive L-DOPA antagonist, when microinjected into depressor sites of the left nucleus tractus solitarii, antagonized depressor responses to mild stimulation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist alone, microinjected bilaterally, elicited a dose-dependent hypertension, which was abolished by alpha-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis seven days after denervation of the left aortic nerve, tyrosine hydroxylase- and L-DOPA-, but not dopamine- and dopamine-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 number of L-DOPA-immunoreactive cells and staining of tyrosine hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that L-DOPA itself is stereoselectively responsible for cardiovascular control in this nucleus, it is probable that L-DOPA is a neurotransmitter of the primary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including depressor neurons of the nucleus tractus solitarii. Endogenously released L-DOPA itself tonically functions to activate depressor neurons for regulation of blood pressure in the rat nucleus tractus solitarii.
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PMID:Baroreceptor-aortic nerve-mediated release of endogenous L-3,4-dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus solitarii of rats. 781 96

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Misu Y. et al. (1996) Prog. Neurobiol. 49, 415-454]. Herein, we attempt to clarify whether lesions in the posterior hypothalamic nucleus decrease the tissue content of L-DOPA in the rostral ventrolateral medulla. We also attempt to clarify whether or not endogenous L-DOPA is evoked by electrical stimulation of the posterior hypothalamic nucleus. It is possible that evoked L-DOPA functions as a transmitter candidate to activate pressor sites of the rostral ventrolateral medulla in anesthetized rats. Electrolytic lesions were made in the bilateral posterior hypothalamic nucleus by a monopolar direct current of 2 mA for 10 s, 10 days before measurements. The effect of the lesions was to selectively decrease the tissue content of L-DOPA by one-half in the right rostral ventrolateral medulla. Decreases in the amounts of dopamine, noradrenaline or adrenaline were not observed. Decreases were also not evident in the right caudal ventrolateral medulla. During microdialysis of the right rostral ventrolateral medulla, extracellular basal levels of L-DOPA and three types of catecholamine were consistently detectable by high-performance liquid chromatography with electrochemical detection. Tetrodotoxin (1 microM) perfused into the right rostral ventrolateral medulla gradually decreased basal levels of L-DOPA by 25%; it decreased basal levels of noradrenaline and adrenaline by 25-30% and dopamine levels by 40%. Intensive electrical stimulation of the ipsilateral posterior hypothalamic nucleus (50 Hz, 0.3 mA, 0.1 ms duration, twice 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 hypertension with only a slight inhibition of tachycardia evoked by stimulation of the posterior hypothalamic nucleus. L-DOPA methyl ester, a competitive L-DOPA antagonist, was bilaterally microinjected into pressor sites of the rostral ventrolateral medulla at 1.5 microg x 2 and 3 microg x 2. The antagonist dose-dependently and consistently antagonized pressor and tachycardiac responses to mild transient stimulation of the unilateral posterior hypothalamic nucleus (33 Hz, 0.2 mA, 0.1 ms duration, for 10 s). In addition, the antagonist alone (3 microg x 2) elicited hypotension and bradycardia. These results show that an L-DOPAergic relay may project from the posterior hypothalamic nucleus directly to pressor sites of the rostral ventrolateral medulla and/or indirectly to certain neurons near pressor sites in microcircuits of the same region. When released, L-DOPA appears to function tonically to activate pressor sites; it also appears to be involved in the maintenance and regulation of blood pressure and heart rate.
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PMID:An L-dopaergic relay from the posterior hypothalamic nucleus to the rostral ventrolateral medulla and its cardiovascular function in anesthetized rats. 1039 36