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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four sulfur-containing analogues of phenylpropylamine were synthesized and evaluated as substrates for dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO). All four phenyl aminoethyl sulfides were shown to be good substrates for DBH whereas only the two analogues not possessing a methyl group alpha to the terminal amino group were substrates for MAO. All four analogues were tested for acute antihypertensive activity in an animal model for hypertension, the spontaneously hypertensive rat (SHR). Two of the analogues, both of which should partition readily across the blood-brain barrier, did not appreciably reduce systemic blood pressure in the 6-h testing period. However, the two analogues that were designed to be relatively restricted to peripheral sites of action caused a dramatic drop in blood pressure in SHR of 25% within 1-1.5-h postinjection, with the analogue designed to be both restricted to the periphery and MAO inactive, causing a more prolonged antihypertensive activity.
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PMID:Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine beta-hydroxylase. 648 71

Plasma dopamine beta-hydroxylase (DBH) activity was estimated in non-pregnant women, normotensive pregnant women during the third trimester and women with pregnancy-induced hypertension (PIH). Non-pregnant women from a high income group had significantly higher DBH activity than their low income counterparts. DBH activity was significantly elevated in women with PIH when compared with non-pregnant and normal pregnant women from a low income group, but was lower than the level in well-nourished, non-pregnant normotensive women.
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PMID:Plasma dopamine beta-hydroxylase activity in pregnancy-induced hypertension. 661 41

The effects of clonidine and minoxidil on sympathetic nervous activity has been studied in 10 patients with accelerated or resistant hypertension. Clonidine 150 to 900 micrograms/day caused a significant decrease in blood pressure of 18.6 mm Hg, of heart rate 16.4 beats/min, of plasma renin activity 1.13ng/ml h, and of urinary noradrenaline excretion 11.55 micrograms/day, and a significant lengthening of the pre-injection period of 12.4 ms. Minoxidil 5 to 22.5 micrograms/day caused a further significant decrease in blood pressure of 24.2 mm Hg, and significant increases in heart rate 8.2 beats/min, plasma renin activity 1.68 ng/ml h and of urinary noradrenaline excretion 5.0 micrograms/day, and a significant shortening of the pre-ejection period of 20.6 ms. Neither clonidine nor minoxidil altered plasma dopamine beta-hydroxylase activity or the cardiovascular responses to treadmill exercise. It is concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.
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PMID:Effect of minoxidil on sympathetic nervous activity in clonidine-treated hypertensive patients. 703 Jul 51

1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/- 1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.
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PMID:Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency. 814 25

The sympathetic nervous system innervates most organs in the body and controls their function. A variety of disease processes, surgery or drugs can result in disordered sympathetic nerve function, which can be either localized or more generalized. Malfunction can result in either sympathetic underactivity (causing postural hypotension, impotence or anhidrosis) or overactivity (causing paroxysmal hypertension or hyperhidrosis). The investigation of sympathetic disorders depends upon the system and organs involved and should include, where relevant, investigation of the possible aetiological processes. The clinical features and management of some of the major disorders affecting the sympathetic nervous system, including the recently described syndrome of DBH deficiency, are described.
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PMID:Sympathetic nervous system disorders in man. 848 87

Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.
Hypertension 1993 May
PMID:Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension. 849 1

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.
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PMID:L-DOPA systems for blood pressure regulation in the lower brainstem. 853 12

Due to more frequent occurrence of the idiopathic arterial hypertension of borderline type (18.97% of screened women), with values varying from 18.7/12.0 to 21.3/12.7 kPa (140/90-160/95 mm Hg), in women chronically exposed to carbon disulfide as compared to the control group (8.5% women), we decided to investigate the activity of sympathetic-adrenal nad serotoninergic systems that play an important role in the haemostasis of cardiovascular system. The aim of the presented study is to evaluate the linear correlation between: 1) serum dopamine-beta hydroxylase activity and the dopamine concentration in plasma as well as 24-hours adrenaline and noradrenaline excretion in the urine; and 2) between catechol-0-methyltransferase and monoaminoxidase activity and the 24-hours excretion of catecholamine in the urine; next the serum and platelet concentration of serotonin and the arterial blood pressure in women chronically exposed to carbon disulfide. The investigations were performed on 140 women, aged 22 to 55, who were divided into two groups: group-I the control group, covered 50 women employed in the Industrial Clothing Factory "Dana" in Szczecin. Group II-the study group, consisted of women employed in the Synthetic Fibres Factory "Wiskord" in Szczecin-Zydowce, in the carbon disulfide (CS2) atmosphere in concentration from 9.36 to 23.4 mg/m3. The microclimate conditions of the production halls in both groups were similar (Tab. 1). It has been observed that in women chronically exposed to CS2 plasma dopamine concentration (p < 0.001) and DBH serum activity (p < 0.001) are significantly lower as compared to the control group parameters (Tab. 2). Also dopamine concentration and DBH activity are lower in all subgroups of women exposed to CS2 (Tab. 3). In women working in the CS2 atmosphere, 24-hours excretion of adrenaline is significantly lower (p < 0.001) as compared to the control group. Parameters for 24-hours noradrenaline and VMA excretion in the urine do not show any statistical significance (Tab. 4). Plasma (p < 0.001) and platelet (p < 0.001) concentration of serotonin is significantly higher in women exposed to CS2. However, 24-hours 5-HIAA excretion in the urine in women of group II is higher than in group I, but does not give evidence of any statistical significance (Tab. 6). Both serum (p < 0.001) and platelet (p < 0.001) MAO activity is significantly lower in women chronically exposed to CS2. Also COMT erythrocyte activity is significantly lower (p < 0.001) in the studied group women (Tab. 8). The women working in the CS2 evaporation display significantly higher serum concentration of total (p < 0.001), bound (p < 0.001) and free (p < 0.001) tryptophane (Tab. 9). In women exposed to CS2, serum concentration of zinc (p < 0.001) and copper ions (p < 0.001) is significantly lower (Tab. 10). In comparison to the control group parameters, the women exposed to CS2 claim values of systolic and diastolic arterial blood pressure being insignificantly higher. However, in women working in CS2 atmosphere the coefficients of linear correlation between plasma (r = 0.59; p < 0.001) and platelet (r = 0.73; p < 0.001) serotonin concentration and the systolic arterial blood pressure, as well as plasma (r = 0.065; p < 0.001) and platelet (r = 0.72; p < 0.001) serotonin concentration and the diastolic arterial blood pressure are significantly higher (Tab. 11). Significantly positive linear correlation between serotonin concentration and arterial blood pressure in women chronically exposed to CS2 may suggest the important role of this amine in the pathogenesis of arterial hypertension.
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PMID:[The influence of chronic exposure to carbon disulfide on metabolism of catecholamines and serotonin in women]. 919 18

Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine and elevates dopamine) in cardiovascular tissues. This study was designed to evaluate the cardiovascular effects of nepicastat. Acute oral administration of nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and positive chronotropic responses to preganglionic sympathetic nerve stimulation (about twofold to sixfold shift in the frequency-response curve) in pithed spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a significant decrease in renal vascular resistance (38%), a tendency toward an increase in renal blood flow (22%), and no adverse effects on urine output and Na/K excretion. In conscious, unrestrained, telemetry-implanted SHRs, nepicastat (30 and 100 mg/kg/day for 30 days) produced dose-dependent decreases in mean arterial blood pressure (peak decrease of 20 and 42 mm Hg, respectively) without evoking reflex tachycardia. Long-term, concurrent administration of nepicastat (30 mg/kg/day, p.o.) and a subthreshold dose of enalapril (1 mg/kg/day, p.o.) produced greater antihypertensive effects than those produced by nepicastat alone. In normal dogs, nepicastat (5.0 mg/kg, p.o., b.i.d., for 4.5 days) blunted the positive chronotropic and pressor response to tyramine. These findings suggest that nepicastat functionally modulates sympathetic drive to cardiovascular tissues and may be of value in the treatment of cardiovascular disorders associated with overactivation of the sympathetic nervous system such as hypertension and congestive heart failure.
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PMID:Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor. 964 84

The purpose of this study is to review the role of dopamine in hypertension and associated conditions. The analysis of literature indicates that present knowledge is mostly based on poor markers and indirect evidence of dopaminergic activity and only few molecular biological data. Alternative markers such as plasma dopamine sulfate emerge as a possible substitute for the low plasma free dopamine detectability, one of the main obstacles in understanding the relationship between circulating dopamine and its receptor actions in hypertension. Essential hypertension represents a heterogeneous entity: based on evidence in borderline and non-modulating hypertension, the tubular dopamine receptor defect may be compensated by increased dopamine synthesis (dopamine beta-hydroxylase suppression-mediated?) and release; alternatively, compatible with data in stable, salt-sensitive and low renin-hypertension, the receptor defect may be amplified by a deficient dopamine synthesis, basal and in response to salt and volume expansion. Secondary forms of hypertension (renovascular, renal, polycystic kidneys, mineralocorticoid, pheochromocytoma) associated conditions (renal and heart failure, diabetes, hypovolaemia, mastocytosis) or iatrogenic (cocaine abuse) are mostly reflected by increased dopamine indices, some of them proposed to be counteracting the activation of prohypertensive mechanisms. In conclusion dopamine should thus be monitored in hypertension while respecting several associated conditions affecting peripheral dopaminergic activity. Catecholamine synthesis and metabolism enzymes' and dopamine receptors' targeting are essential for advancing the understanding of dopamine's diagnostic and therapeutic implications.
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PMID:Peripheral dopamine in hypertension and associated conditions. 1048 70


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