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)

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

We report a 67-year-old man with rt. hand resting tremor and rigidity after lt. putaminal hemorrhage. He had hypertension and alcoholic liver cirrhosis as past history. When he was 62 years old, he realized rt. hemiplegia suddenly and admitted in Juntendo Urayasu hospital. Brain CT showed intracranial hemorrhage in lt. putamen. He was treated with neurosurgery operation for rejecting hemorrhage. Mild rt. hemiparesis remained but he could live independently. He was medicated sulpiride for depression after cerebrovascular accident. On 63 years old, resting tremor and rigidity appeared on his rt. hand. His doctor stopped sulpiride and treated with L-Dopa/Benserazide and trihexiphenidyl. His parkinsonism was stable with this treatment for four years. His doctor considered that he was Parkinson's disease or drug-induced parkinsonism. On 67 years old, he became akinetic-mutism state suddenly and admitted in the hospital. His consciousness turned alert soon and discharged after two weeks. This episode was considered as epilepsy. After one week from discharge, he was found cardio-pulmonary arrest and confirmed dead in the hospital. Post-mortem examination revealed necrosis in the posterior-lateral part of lt. putamen due to hemorrhage. However, there was no degenerative change of the striatum or the substantia nigra and no Lewy bodies in his brain. Other pathological changes were also not found. His parkinsonism might be caused putaminal pathology due to hemorrhage.
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PMID:[A 67-year-old man with rt. hand resting tremor and rigidity after lt. putaminal hemorrhage]. 1591 60

Pheochromocytomas/paragangliomas(PHEOs/PGLs) are rare but treacherous catecholamine-producing tumors which, if overlooked or improperly treated, will almost invariably prove fatal. Patients with MEN2 PHEOs have a high incidence of paroxysmal attacks and a higher prevalence of hypertension and other cardiovascular problems than do patients with Von-Hippel-Lindau (VHL) PHEOs. Compared to measurements of deconjugated metanephrines, plasma concentrations of free metanephrines are relatively independent of renal function and therefore more suitable for diagnosis of PHEO/PGL. Recently, the focus of Positron Emission Tomography (PET) imaging for these tumors has been the localization of PHEO. Although a limited number of studies are available, [18F]-fluorodopamine ([18F]DA) PET has been found to be the best overall imaging modality in the localization of PHEO. For adrenal PHEOs, this method seems to be comparable to other functional modalities such as [18F]-fluorodopa ([18F]DOPA) PET or [123I]-metaiodobenzylguanidine ([123I]MIBG)scintigraphy. For extraadrenal PHEOs, data are limited and more extensive studies are needed. In patients with metastatic PHEO, the sensitivity of [18F]DA PET is superior to [123I]MIBG. The so called "flip-flop" imaging showing superiority of non-specific [18F] flurodeoxyglucose (FDG) PET over specific [18F]DA PET has been described in rapidly progressive, often metastatic SDHB-associated PHEOs. Whether these data reflect PHEO cell dedifferentiation (e.g. losing Norepinephrine Transporter-NET) or increased metabolic rate remains to be established.
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PMID:Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. 1957 Jul 38

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas.
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PMID:Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome. 2156 41

Several clinical and animal studies suggest that "blood pressure goes with the kidney," that is, a normotensive recipient of a kidney genetically programmed for hypertension will develop hypertension. Intrarenal dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport. The candidate transport systems for L-DOPA, the source for dopamine, include the sodium-dependent systems B(0), B(0,+), and y(+)L, and the sodium-independent systems L (LAT1 and LAT2) and b(0,+). Renal LAT2 is overexpressed in the prehypertensive spontaneously hypertensive rat (SHR), which might contribute to enhanced L-DOPA uptake in the proximal tubule and increased dopamine production, as an attempt to overcome the defect in D1 receptor function. On the other hand, it has been recently reported that impaired arginine transport contributes to low renal nitric oxide bioavailability observed in the SHR renal medulla. Here we review the importance of renal amino acid transporters in the kidney and highlight pathophysiological changes in the expression and regulation of these transporters in essential hypertension. The study of the regulation of renal amino acid transporters may help to define the underlying mechanisms predisposing individuals to an increased risk for development of hypertension.
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PMID:Renal amino acid transport systems and essential hypertension. 2361 67

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson's disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC) class (p<0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2-17; p<0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p=0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications.
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PMID:Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson's disease. 2491 57

According to the catecholaldehyde hypothesis, the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) contributes to the loss of nigrostriatal dopaminergic neurons in Parkinson's disease. Monoamine oxidase-A (MAO-A) catalyzes the conversion of intraneuronal dopamine to DOPAL and may serve as a therapeutic target. The "cheese effect"-paroxysmal hypertension evoked by tyramine-containing foodstuffs-limits clinical use of irreversible MAO-A inhibitors. Combined MAO-A/B inhibition decreases DOPAL production in rat pheochromocytoma PC12 cells, but whether reversible MAO-A inhibitors or MAO-B inhibitors decrease endogenous DOPAL production is unknown. We compared the potencies of MAO inhibitors in attenuating DOPAL production and examined possible secondary effects on dopamine storage, constitutive release, synthesis, and auto-oxidation. Catechol concentrations were measured in cells and medium after incubation with the irreversible MAO-A inhibitor clorgyline, three reversible MAO-A inhibitors, or the MAO-B inhibitors selegiline or rasagiline for 180 minutes. Reversible MAO-A inhibitors were generally ineffective, whereas clorgyline (1 nM), rasagiline (500 nM), and selegiline (500 nM) decreased DOPAL levels in the cells and medium. All three drugs also increased dopamine and norepinephrine, decreased 3,4-dihydroxyphenylalanine, and increased cysteinyl-dopamine concentrations in the medium, suggesting increased vesicular uptake and constitutive release, decreased dopamine synthesis, and increased dopamine spontaneous oxidation. In conclusion, clorgyline, rasagiline, and selegiline decrease production of endogenous DOPAL. At relatively high concentrations, the latter drugs probably lose their selectivity for MAO-B. Possibly offsetting increased formation of potentially toxic oxidation products and decreased formation of DOPAL might account for the failure of large clinical trials of MAO-B inhibitors to demonstrate slowing of neurodegeneration in Parkinson's disease.
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PMID:Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells. 2657 16

Renalase is a newly-discovered enzyme--amine oxidase containing flavin adenine dinucleotide that determines its activity. Kidneys are the main source of renalase, however, the enzyme has also been detected in the myocardium, skeletal muscles, small intestine, peripheral nerves, adrenal cortex and adipose tissue. This enzyme metabolizes circulating catecholamines, particularly epinephrine and L-3,4-dihydroxyphenylalanine (a dopamine precursor). For this reason, it is considered that renalase may play a significant role in the regulation of blood pressure. There are some factors enhancing the release of renalase: rising catecholamines levels in the circulation and increase in blood pressure. Experimental and clinical studies revealed renalase deficiency in chronic kidney disease (CKD) and hypertension. In contrast, the results of assays based on currently available ELISA kits demonstrate an increase in renalase concentration in patients with CKD. On the basis of currently available studies it is difficult to determine how important are changes in the expression and secretion of renalase in the pathogenesis of hypertension in CKD patients. Stimulation of catecholamines degradation, perhaps using recombinant renalase or its analogues, is a new concept in the treatment of hypertension in CKD.
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PMID:[Renalase and its role in the development of hypertension in patients with chronic renal failure]. 2681 39

Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension.
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PMID:Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA. 2778 Aug 18


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