UMLS:C0085580 - FACTA Search

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Query: UMLS:C0085580 (essential hypertension)
14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A clinical study of pyratrione, a tyrosine hydroxylase inhibitor, has been carried out in essential hypertension. 2. Out of thirty-nine patients who received pyratrione, twenty-eight showed a significant decrease in blood pressure.
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PMID:Effect of pyratrione (a tyrosine hydroxylase inhibitor) in essential hypertension. 2 76

The concentration of plasma catecholamines (CA), serum dopamine beta-hydoxylase (DBH) activity and plasma renin activity (PRA) were simultaneously measured in 55 patients with essential hypertension (EH). Further the enzyme activities of CA biosynthesis in human vas deferens excised at elective vasectomy were related with the blood pressure, plasma CA, serum DBH of 57 men at the time of vasectomy. Total plasma CA and norepinephrine (NE) were increased in 28 and 35% of patients with benign EH, respectively. Total plasma CA were also increased in 45% of men with elevated blood pressure prior to vasectomy. Total plasma CA were correlated with diastolic blood pressure in EH (p less than 0.01). Further, in men with normal and raised blood pressure prior to vasectomy, there was a significant correlation of total plasma CA with systolic and diastolic blood pressure (p less than 0.01). Total plasma CA were correlated with PRA in patients with EH (r=0.497, p less than 0.001). Capacity for NE biosynthesis, vas deferens tyrosine hydroxylase (TYH) activity and dopa decarboxylase (DDC) activity were increased in men with raised blood pressure. There was a direct correlation of total plasma CA with the activities of TYH and DDC (r=0.46, and 0.54, p less than 0.005). Increased sympathetic nerve tonicity associated with increased neurotransmitter biosynthesis may be an important factor responsible for blood pressure elevation in men prior to vasectomy and in others with EH. The some patients with EH may have a renin-catecholamine relationship and both pressor systems may be linked to be a pathogenic factor for the elevation of blood pressure.
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PMID:Biochemical evaluation of sympathetic nerve tone in essential hypertension. 23 60

The metabolic fate of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (alpha-MPT), was studied after oral administration of single and multiple doses to patients with pheochromocytoma and essential hypertension. No major urinary excretion product was found other than the drug itself, which accounted for 44-88% of the fate of single or repeated oral doses. Though less than 1% of the administered drug could be recovered in the urine as catechol metabolites, it was possible to identify alpha-methyldopa, alpha-methyldopamine, and alpha-methylnorepinephrine and to quantify the excretion of the first two of these compounds. This minor route of metabolism required revision of methodology (presented herein) for measuring urinary catecholamines during alpha-MPT treatment since these compounds produce spurious fluorescence in routine methods of assay for catecholamines. The catechol metabolites probably are not present in sufficient amounts to contribute to the biochemical effects of the drug. Determination of plasma concentrations of alpha-MPT during maintenance therapy and considerations of the kinetics of enzyme inhibition enabled a calculation to be made of the degree of inhibition of catecholamine synthesis to be expected in the patient. This was calculated to be about 75% for the highest doses employed and is similar in magnitude to experimentally determined values.
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PMID:Metabolism of alpha-methyltyrosine in man: relationship to its potency as an inhibitor of catecholamine biosynthesis. 563 44

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.
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PMID:[Dopamine and hypertension]. 826 73

To investigate the peripheral dopaminergic modulation in the pathogenesis of human hypertension, we examined the responses of plasma free dopamine (DA) to dexamethasone (Dx) administration, which is suggested to activate dopaminergic activity. We administered Dx 2 mg intravenously to patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT). Plasma free DA was increased significantly in all groups and the responses were more remarkable in PA than in EH and NT. Plasma epinephrine (E) showed a gradual increase while plasma norepinephrine (NE) tended to decrease in all groups. The responses of both plasma DA and E were completely blocked by 250 mg of alpha-methyl-p-tyrosine, a tyrosine hydroxylase (TH) inhibitor, suggesting that Dx may stimulate peripheral dopaminergic activity by increasing catecholamine synthesizing enzyme (probably TH) activities. These data suggest that DA itself plays an inherent role in the sympathoadrenal regulation rather than only as a precursor of NE and that dopaminergic hyperresponses may be involved in the pathophysiology of PA.
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PMID:Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in hypertensive patients. 852 61

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma. There was a weak but significant correlation between the values of PDA and DA sulfate measured in the same specimens, but DA sulfate was more susceptible to impaired renal function. Upright posture, high salt diets and an intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but significant increase in PDA in normal and hypertensive subjects. An intravenous dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after medication, which was completely blocked by concomitant administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both high salt diets and MCP were blunted in salt-sensitive patients with uncomplicated essential hypertension. The results suggest that DA is not only a precursor of norepinephrine biosynthesis but also plays an inherent role as an active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is a sensitive marker of peripheral dopaminergic activity, which may operate to modulate the cardiovascular and endocrine functions and participate in the pathogenesis of some types of hypertension.
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PMID:Plasma free dopamine: physiological variability and pathophysiological significance. 852 77

Despite advances in the understanding of monogenic hypertensive disorders, the genetic contribution to essential hypertension has yet to be elucidated. The position of tyrosine hydroxylase (TH) as the rate-limiting enzyme in catecholamine biosynthesis renders it a candidate gene for the etiology of hypertension. The TH gene contains an internal, informative microsatellite marker (TCAT)9. We undertook (1) an association study in a group of well-characterized hypertensive subjects (HT) and control subjects (NT) and (2) an affected sibling pair (ASP) study using sibships from our local family practices. Two hundred twenty-seven hypertensive patients (pretreatment systolic/diastolic blood pressure [BP] range, 139/94 to 237/133 mm Hg; age range [SD], 30 to 71 [8.5] years) were age- and gender-matched with 206 control subjects (BP range, 96/62 to 153/86 mm Hg; age range, 40 to 70 [7.6] years). One hundred thirty-six affected sibling pairs were recruited for our linkage study; 73 young borderline hypertensive subjects (YHT) (pretreatment BP range, 123/76 to 197/107 mm Hg; age range, 20 to 51 [9.4] years) were also recruited in whom recent pretreatment norepinephrine and epinephrine levels were available. All subjects were white. The TH short tandem repeat (STR) was amplified using specific polymerase chain reaction cycling conditions in all subjects, and products were run on an ABI 373A sequencer. TH alleles were assigned using Genescan and Genotyper software. Five TH alleles were present and designated A through E. Allele frequencies in the NT population (A, B, C, D, and E: 0.24, 0.17, 0.13, 0.20, and 0.26, respectively) were significantly different from the HT cohort (A, B, C, D, and E: 0.24, 0.19, 0.11, 0.11, and 0.35, respectively), P<0. 0005 (Pearson's test chi2=19.94; 4 df). The E allele appears overrepresented in the HT group, whereas the D allele appears to be overrepresented in the NT group. TH genotype frequencies were also significantly different between cases and controls (P<0.001; chi2=36. 57; 14 df). Both groups were in Hardy-Weinberg proportion. There was a trend (NS) for the D allele to be associated with a lower BP when BP was analyzed as a quantitative trait. ASP linkage data was analyzed using Splink, a nonparametric program. Expected values for sharing 0, 1, and 2 alleles (Z0, Z1, and Z2, respectively) may be expected to be 25%, 50%, and 25%, respectively, by chance (assuming identity by descent). These probabilities were calculated by Splink as 34, 68, and 34, respectively, and compared with observed values of 36.8, 67.9, and 31.3, respectively; thus, there was no excess sharing of TH alleles among affected sibling pairs (P=0.59; logarithm of odds ratio score, 0.0). TH allele frequencies in our YHT group (A, B, C, D, and E: 0.24, 0.20, 0.12, 0.15, and 0.29, respectively) were similar to those of our NT cohort (P>0.05). There was a trend for lower pretreatment plasma norepinephrine levels with the D allele in this YHT cohort. A common and potentially functional variant at codon 81(Val-->Met) within exon 2 of the TH gene (which we show to be in linkage disequilibrium with TH-STR) was also typed in our YHT but did not associate with catecholamine levels and is therefore unlikely to account for our findings with D and E TH-STR. In conclusion, the TH locus strongly associates with essential hypertension in a case-control model using well-characterized hypertensive and control groups. An ASP linkage model was negative, presumably because of lack of power. This study suggests that the TH gene, or a nearby gene, may be involved in the etiology of essential hypertension.
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PMID:Positive association of tyrosine hydroxylase microsatellite marker to essential hypertension. 977 62

Von Euler characterised the sympathetic neurotransmitter noradrenaline (NA) and postulated that excessive neural tone was a cause of primary hypertension (PH). Thirty years ago, we found raised NA levels in 30-40% of young patients with PH. Laragh found plasma renin activity (PRA) a risk marker for coronary artery disease. With Esler, Miura, and Campese, a close association was found of plasma NA with PRA. We found raised tyrosine hydroxylase activity (AC) in the hearts of a rabbit model of sinoaortic denervated hypertension and in PH with raised plasma NA. Esler utilised titrated NA infusion and described increased spillover of NA from heart, kidney and subcortical areas of brain of patients with PH. With Eide we found raised cerebrospinal fluid (CSF) NA in PH (not secondary hypertension) and with Kolloch and Miura, we found raised plasma/CSF NA in conjunction with reduced dopaminergic tone. With Shkvatsabaya, Yurenev and Davison, we found that relaxation therapy improved the anger ambience and blood pressure of PH with raised plasma NA vs those with normal NA levels. Campese found a hypothalamic source of raised blood pressure in two rat models - microphenol treated and ischaemic kidney. The resulting hypertension was associated with raised NA turnover of their hypothalamic centres. Finally, with Hsueh and Hodis, we found raised plasma NA in association with insulin resistance increased left ventricular mass and intimal medial hypertrophy in Mexican-American diabetics and their yet unaffected offspring. Reliable estimates of human sympathetic AC, including levels of plasma NA in the effluent of selected organs and peripheral venous and arterial sites, may eventually be displaced by techniques using genetic analysis and molecular biology. Never the less, the sympathetic nervous system appears to play an important role in the pathogenesis, sequelae and therapy of PH.
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PMID:The sympathetic nervous system: the muse of primary hypertension. 1198 98

TH01 is a tetrameric short tandem repeat locus located in intron 01 of the tyrosine hydroxylase gene. The tyrosine hydroxylase catalyzes the hydroxylation of L-tyrosine to L-DOPA and is the rate limiting enzyme in the synthesis of catecholamines like noradrenaline or adrenaline, which are pivotal in the regulation of blood pressure. In a clinical study a strong correlation between alleles *9.3 and *10 and essential hypertension was observed ([2] Hypertension 32: 676-682). To further investigate this association, we typed TH01 in 296 autopsy cases and correlated the genotypes to the heart weight as parameter for myocardial hypertrophy. No significant correlation was observed. Moreover, dividing the studied cases into 2 groups, one including 172 casualties from hypertension-associated diseases (myocardial infarction, left heart failure, aortic aneurysm, spontaneous intracerebral bleeding and cerebral infarction) and one consisting of 124 cases of death unrelated to hypertension, revealed similar allelic frequencies for both groups. Our data thus suggest that TH01 long alleles appear not to lead to a significant increase in the incidence of myocardial hypertrophy or other hypertension associated diseases. This could be explained by a relatively small impact of the TH01 genotype on the blood pressure or by counteraction of another mechanism related to catecholamines and their effect on the human body.
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PMID:TH01, a tetrameric short tandem repeat locus in the tyrosine hydroxylase gene: association with myocardial hypertrophy and death from myocardial infarction? 1573 19

Higher activity of the peripheral sympathetic nervous system, accompanied by higher tyrosine hydroxylase activity is frequently and consistently reported in human essential hypertension as well as in animal models of hypertension. However, results obtained in the adrenals, particularly in young animals before the development of hypertension, are scarce and controversial. In the present study tyrosine hydroxylase activity and catecholamine content in the adrenals of spontaneously hypertensive rats and of age-matched control Wistar Kyoto rats were evaluated before, during and after the development of hypertension (5, 12 and 22-week-old animals). Results show that both tyrosine hydroxylase activity and total amine content in the adrenals of spontaneously hypertensive rats were significantly reduced (35% reduction) at all studied ages. Determination of the kinetic parameters for tyrosine hydroxylase in the adrenals of 5 week-old spontaneously hypertensive rats revealed a 38% reduction in V(max) values (13.4 versus 21.3 nmol L-DOPA/mg prot/h in age-matched controls) accompanied by lower levels of expression of both tyrosine hydroxylase total protein and phosphoSer40 observed by Western-Blot. In contrast, norepinephrine content in both plasma and tail artery were significantly higher in the spontaneously hypertensive strain. In conclusion, contrary to the higher peripheral sympathetic activity, tyrosine hydroxylase activity and catecholamine content in the adrenals of spontaneously hypertensive rats are markedly reduced before, during and after the development of hypertension. End product, long-term feedback inhibition by the high norepinephrine plasma levels could be responsible for this reduction, establishing yet another regulatory mechanism of tyrosine hydroxylase operating in adrenal cromaffin cells.
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PMID:Decreased tyrosine hydroxylase activity in the adrenals of spontaneously hypertensive rats. 1582 May 6

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