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

By microdialysis in the rostral ventrolateral medulla (RVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (DOPA) release was partially Ca(2+)-dependent and tetrodotoxin-sensitive and was markedly reduced by alpha-methyl-p-tyrosine (alpha-MPT; 200 mg/kg, i.p.). K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By microinjections into unilateral RVLM, L-DOPA (30-300 ng) produced dose-dependent hypertension and tachycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6-hydroxydopamine. These responses were antagonized by L-DOPA methyl ester (1.5 micrograms), a competitive L-DOPA antagonist. D-DOPA, dopamine, noradrenaline or adrenaline (300 ng) produced no effect. Furthermore, L-DOPA methyl ester alone microinjected into bilateral RVLM (2 micrograms x 2) produced prolonged hypotension and bradycardia, which were abolished by alpha-MPT. These data suggest that L-DOPA is relevant to modulation of sympathetic activity in the rat RVLM.
 ...
PMID:Evidence for L-dopa relevant to modulation of sympathetic activity in the rostral ventrolateral medulla of rats. 790 2

Dopamine has been well recognized to be a precursor of norepinephrine, exhibiting cardiovascular effects through alpha-adrenoceptor stimulation by norepinephrine production and release in sympathetic nerve endings. It also has the specific and unique effects of natriuresis and vasodilation. Since dopamine is one of the important endogenous hypotensive and natriuretic substances, it is speculated that impaired dopamine generation and/or the disturbance of the effects of dopamine could cause hypertension with suppression of plasma renin activity and/or salt-sensitivity. A non-specific enzyme of aromatic L-amine acid decarboxylase (AAAD) converting from 3,4-dihydroxyphenylalanine (DOPA) to dopamine is widely distributed in the peripheral tissue, e.g. the sympatho-adrenomedullary system, the small intestine, the lung, the liver, the kidney, etc. Since tyrosine hydroxylase is a rate-limiting enzyme of catecholamine biosynthesis, DOPA generation in the neuronal tissues is accelerated with the sympathetic nerve activation by stress such as emotional and environmental changes, resulting in an increase of DOPA delivery to the non-neuronal tissues containing non-neuronal AAAD. More than five receptors for dopamine are cloned in the brain, and it is suggested that more than three different types of dopamine receptors are in the peripheral tissues. In spontaneously hypertensive rats, the post-receptor defect of renal dopamine D1-receptor has been proposed where peripheral dopamine generation compensatorily increased. In Dahl salt-sensitive rats, another model of genetic hypertension, the blunted response of urinary dopamine to sodium loading has been demonstrated. It is controversial whether abnormalities of the neuronal and/or non-neuronal (particularly renal) dopamine system play a contributory role on the pathogenesis of essential hypertension. However, it is plausible that the impairment of dopamine generation and/or the defective responses of a dopamine receptor might induce sodium retention and hypertension.
 ...
PMID:[Dopamine and hypertension]. 826 73

By microdialysis in the unilateral caudal ventrolateral medulla (CVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (L-DOPA) release was in part tetrodotoxin-sensitive or Ca(2+)-dependent and was abolished by i.p. alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase inhibitor. High K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By unilateral microinjections into the CVLM, L-DOPA (10-100 ng) produced dose-dependent, marked hypotension and bradycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6-hydroxydopamine. These responses were antagonized by L-DOPA methyl ester, a competitive L-DOPA antagonist. A depressor response to dopamine or noradrenaline (100 ng) was far smaller and slower in onset than that to L-DOPA (30 ng). D-DOPA (100 ng) produced no effect. Furthermore, L-DOPA methyl ester microinjected into bilateral CVLM produced some hypertension and tachycardia, which were markedly reduced by alpha-MPT. Transmitter-like L-DOPA tonically functions to mediate vasodepressor control in CVLM of rats.
 ...
PMID:Transmitter-like L-3,4-dihydroxyphenylalanine tonically functions to mediate vasodepressor control in the caudal ventrolateral medulla of rats. 826 47

Juvenile spontaneously hypertensive rats (SHR) have higher plasma levels of catechols and markedly larger catechol responses to yohimbine than do normotensive Wistar-Kyoto rats, indicating increased sympathoadrenal outflow and increased alpha 2-adrenergic receptor-mediated restraint of peripheral catecholamine release during hypertension development in SHR. Yohimbine-induced catecholamine release and metabolism in the posterolateral hypothalamus of the brain were assessed in juvenile (6 to 7 weeks) and adult (15 to 16 weeks) SHR and Wistar-Kyoto rats. In vivo microdialysis was used to obtain samples for measurements of norepinephrine, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid in conscious animals before and after yohimbine injection (1 mg/kg IV) beginning 24 hours after probe implantation. Catecholamine synthesis was examined from elevations of 3,4-dihydroxyphenylalanine levels after probe perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. In adults, SHR had higher dialysate norepinephrine (277 +/- 38 versus 181 +/- 35 pg/mL), dihydroxyphenylglycol (3260 +/- 509 versus 2231 +/- 201 pg/mL), methoxyhydroxyphenylglycol (2659 +/- 369 versus 1890 +/- 144 pg/mL), and dihydroxyphenylacetic acid (46,312 +/- 5512 versus 13,187 +/- 1963 pg/mL) levels and markedly larger increases in 3,4-dihydroxyphenylalanine levels after NSD-1015 than Wistar-Kyoto rats. In juveniles, SHR had larger proportionate increments in microdialysate norepinephrine levels after yohimbine than Wistar-Kyoto rats (85% versus 25%). Although juvenile SHR and Wistar-Kyoto rats had similar NSD-1015-elicited increments in 3,4-dihydroxyphenylalanine levels, systemic yohimbine enhanced the NSD-1015-elicited 3,4-dihydroxyphenylalanine elevations in juvenile SHR but not in Wistar-Kyoto rats. These findings suggest augmented norepinephrine release and catecholamine synthesis in the posterolateral hypothalamus of adult SHR and augmented alpha 2-adrenergic receptor restraint of both norepinephrine release and catecholamine synthesis in juvenile SHR.
Hypertension 1993 Oct
PMID:In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats. 840 51

Central autonomic dysfunctions can be due to primary (degenerative) or secondary disorders. Autonomic failure (AF) may be a major manifestation of multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). In both MSA and IPD, AF is almost invariably associated with neuronal loss in the intermediolateral cell columns. Dysautonomia in MSA is early, severe, and progressive, including marked orthostatic hypotension and urinary incontinence and is complicated by respiratory disturbances, such as laryngeal stridor and sleep apnea. MSA/AF can be differentiated from primary (or pure) autonomic failure (PAF) without central nervous system involvement. PAF is mainly a disorder of the postganglionic neurons. In contrast to PAF, MSA/AF has preserved basal sympathetic activity, decreased cerebrospinal fluid (CSF) neurotransmitter markers, impaired vasopressin response to hypotension, and impaired adrenocorticotrophic hormone/beta endorphin response to hypoglycemia. AF in IPD is generally less severe than in MSA. Poor response to L-Dopa, abnormal urethral sphincter electromyography, and CSF markers may distinguish MSA from IPD. Secondary autonomic disorders may result from traumatic, vascular, inflammatory, demyelinating, or neoplastic lesions involving corticolimbic, hypothalamic, brainstem, or spinal autonomic network. These disorders can cause AF or autonomic hyperactivity, such as arrhythmia, hypertension, and hyperthermia. However, many disorders may only produce subclinical abnormalities.
 ...
PMID:Central autonomic disorders. 845 95

We have explored probable neurotransmitter roles of L-3,4-dihydroxyphenylalanine (L-DOPA) in baroreceptor reflex and blood pressure regulation in depressor sites of the nucleus tractus solitarii (NTS) and the caudal ventrolateral medulla (CVLM), and in pressor sites of the rostral ventrolateral medulla (RVLM) in anesthetized rats. During microdialysis of these three areas, the basal L-DOPA release is in part tetrodotoxin (TTX)-sensitive and Ca2(+)-dependent, high K+ Ca2(+)-dependently releases dL-DOPA. L-DOPA microinjected (10-300 ng) dose-dependently produces postsynaptic depressor responses in the NTS and CVLM and pressor responses in the RVLM, and a recognition site for L-DOPA functions tonically to activate depressor neurons in the NTS and CVLM and pressor neurons in the RVLM. It is highly probable that L-DOPA is a neurotransmitter of the baroreceptor afferents terminating in the NTS, which is based on further findings such as (1) antagonism by a competitive L-DOPA antagonist against depressor responses to aortic nerve stimulation, (2) TTX-sensitive L-DOPA release by aortic nerve stimulation, (3) abolition of baroreceptor-stimulated L-DOPA release by bilateral sino-aortic denervation and (4) decreases in tyrosine hydroxylase (TH)- and L-DOPA-immunoreactivities without modifications of dopamine- and DBH-immunoreactivities in the left NTS and ganglion nodosum 7 days after ipsilateral aortic nerve denervation peripheral to the ganglion. In the NTS, GABA tonically functions to inhibit via GABAA receptors L-DOPA release and depressor responses to L-DOPA, whereas L-DOPA induces GABA release. Impaired TTX-sensitive neuronal activity to release L-DOPA in the NTS and enhanced TTX-sensitive neuronal activity including a decrease in decarboxylation of L-DOPA to dopamine and an increase in sensitivity of the recognition site to L-DOPA in the RVLM are relevant to the maintenance of hypertension in spontaneously hypertensive rats. Decreases in the contents of L-DOPA in the right CVLM 10 days after electrical lesion of the ipsilateral NTS suggest a 'L-DOPAergic' and monosynaptic relay from the NTS to the CVLM. L-DOPA seems to play major roles as a neurotransmitter for baroreceptor reflex and blood pressure regulation in the lower brainstem of rats.
 ...
PMID:L-DOPA systems for blood pressure regulation in the lower brainstem. 853 12

Experiments were designed to clarify whether a tonic L-DOPA system is altered in the caudal ventrolateral medulla (CVLM) of adult spontaneously hypertensive rats (SHR), compared to age-matched Wistar-Kyoto rats (WKY). By microdialysis in CVLM, basal L-DOPA release was constantly detectable and was lower in SHR than that in WKY. This release was reduced by tetrodotoxin perfusion (1 microM) in WKY to a basal level in SHR, whereas no modification occurred with tetrodotoxin in SHR. No difference of tyrosine hydroxylase and DOPA decarboxylase activities in the CVLM region was seen between the two strains. By microinjections into depressor sites of CVLM, L-DOPA (10-300 ng) or L-glutamate (3-300 ng) elicited dose-dependent depressor and bradycardic responses and greater depressor responses to both amino acids were seen at high doses in SHR, compared to WKY. Tonic neuronal activity to release L-DOPA is lost in the CVLM of adult SHR and this loss may contribute to maintenance of hypertension in SHR.
 ...
PMID:Loss of tonic neuronal activity to release L-DOPA in the caudal ventrolateral medulla of spontaneously hypertensive rats. 857 91

Recent findings have enhanced our understanding of the roles played by the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the lower brainstem. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in depressor sites of the nucleus tractus solitarii (NTS). It also seems to be a neurotransmitter in depressor sites of the caudal ventrolateral medulla (CVLM) and in pressor sites of the rostral ventrolateral medulla (RVLM) of normotensive Wistar rats. We have explored whether or not presynaptic and postsynaptic functions of the L-DOPA system in these areas are altered to maintain hypertension in adult spontaneously hypertensive rats, as compared with age-matched Wistar Kyoto rats. In this review article, we survey the roles of the L-DOPA system in the baroreceptor reflex and in blood pressure regulation in the rat lower brainstem.
 ...
PMID:Altered L-DOPA systems for blood pressure regulation in the lower brainstem of spontaneously hypertensive rats. 874 4

L-DOPA administration to 21--25-day-old rats with inherited stress-induced arterial hypertension (ISIAH rats)lowered arterial pressure both at rest and in emotional stress in adult rats. The effect seems to be due to enhancement of the brain catecholamine synthesis rather than the peripheral one in early ontogenesis. The long-term hypotensive effect of the L-DOPA was supposed to be caused in part by changes revealed in the brain catecholaminergic system.
 ...
PMID:[The brain catecholaminergic system during the long-term correction of hereditary arterial hypertension]. 882 84

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.
 ...
PMID:Neurobiology of L-DOPAergic systems. 889 95


<< Previous 1 2 3 4 5 6 7 8 Next >>