UMLS:C0020538 - FACTA Search

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

A series of experiments was designed to explore the mechanisms contributing to hypertension caused by an acute or chronic sodium load. Acute salt-loading in totally or subtotally nephrectomized animals caused hypertension mediated partly through stimulation of excessive vasopressin release and partly through adrenergic stimulation. Chronic high-salt diet in rats submitted to partial nephrectomy, mineralocorticoid excess or one-kidney-one-clip renovascular hypertension caused blood pressure elevation mediated through a central neurogenic mechanism that could be reversed by administration of an inhibitor of phenylethanolamine-N-methyltransferase, the enzyme catalyzing conversion of norepinephrine to epinephrine. Thus, two vasopressor mechanisms were stimulated by sodium excess: an acute, transient, partly vasopressin-mediated phase seemed to be followed by a chronic phase mediated through stimulation of central sympathetic neurons. In neither phase was blood pressure related to intravascular fluid volume expansion.
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PMID:Possible mechanisms of sodium-dependent hypertension: volume expansion or vasoconstriction? 710 37

We evaluated the activity of phenylethanolamine-N-methyltransferase (PNMT) and dopamine-beta-hydroxylase (DBH) in 16 pheochromocytomas. Ten of the tumors were from patients with Multiple Endocrine Neoplasia and six of the tumors were from patients with sporadic pheochromocytomas. All of the pheochromocytomas contained PNMT and DBH activity. There was a significant correlation between PNMT activity and epinephrine concentration in the pheochromocytomas (r=0.61); there was no significant correlation between PNMT activity and norepinephrine concentration (r=0.38) or DBH activity and norepinephrine (r=0.06) or dopamine (r=0.31) concentration. In general, the patients with the highest PNMT activity in their pheochromocytomas tended to have paroxysmal (rather than sustained) hypertension and to excrete more E than NE in their urine.
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PMID:Phenylethanolamine-N-methyltransferase activity determines the epinephrine concentration of pheochromocytomas. 732 41

Glomus jugulare tumors have been reported to secrete norepinephrine and cause severe hypertension with features similar to pheochromocytoma. In contrast, epinephrine secretion has not been observed in these neoplasms. This has been attributed to the absence of the norepinephrine-methylating enzyme, phenylethanolamine-N-methyltransferase (PNMT), required for epinephrine synthesis. We report a patient with severe hypertension caused by a glomus tumor that secreted norepinephrine and epinephrine. Following selective venous sampling, catecholamines were quantified by radioenzymatic assay. Marked elevations in norepinephrine and epinephrine release were localized to the glomus tumor. The enzymes involved in catecholamine biosynthesis, including PNMT and tyrosine hydroxylase, were identified immunocytochemically in the tumor. The glomus tumor had staining patterns identical to those observed within normal rat glomus cell. Hypertension resolved with resection of the functioning tumor. This is the first report of PNMT in a functioning paraganglioma of the glomus jugulare region. The factors that determine why functional activity is expressed only rarely by paraganglioma remain undefined.
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PMID:Hypertension and a tumor of the glomus jugulare region. Evidence for epinephrine biosynthesis. 813 4

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

Neurons in rat medulla oblongata with Fos immunoreactivity as a marker of synaptic excitation evoked by pentylenetetrazole-induced seizures were compared with cell populations activated by the stimulation of chemoreceptor and baroreceptor afferent pathways. Chemoreceptors were stimulated by placing rats in a hypoxic gas mixture (7% oxygen) for 2 h. Baroreceptors were activated by phenylephrine-induced hypertension. Seizures and hypoxia induced Fos immunoreactivity in neurons with similar anatomical distributions in the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and ventrolateral medulla. Hypertension was associated with Fos immunoreactivity in an overlapping anatomical distribution compared to seizures and hypoxia, but in a more restricted pattern. A similar proportion of catecholaminergic cells of medulla oblongata (cells immunoreactive for catecholamine synthetic enzymes, tyrosine hydroxylase or phenylethanolamine-N-methyltransferase) had Fos immunostaining after seizures and hypoxia (P > 0.05), while significantly fewer were activated by hypertension (P < 0.05). The majority of tyrosine hydroxylase-immunoreactive cells in caudal ventrolateral medulla were activated by both seizures and hypoxia (mean per cents, 79 and 67%, respectively). Since cell populations activated by seizures and hypoxia are indistinguishable, and a majority of tyrosine hydroxylase-reactive cells in caudal ventrolateral medulla are independently activated by each stimulus, it may be inferred that some impulses originating from seizures and chemoreceptor afferent pathways converge to a common set of neurons. These observations identify neurons in rat medulla oblongata which may mediate the impact of seizures on central processing of chemoreceptor afferent activity.
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PMID:Comparison of neurons in rat medulla oblongata with fos immunoreactivity evoked by seizures, chemoreceptor, or baroreceptor stimulation. 880

The rostral ventrolateral medulla (RVLM) is part of the vasomotor centre which controls the cardiovascular system and may therefore be critical to the genesis of postoperative hypertension. This area is probably a common site of termination of different inputs involved in the baroreflex. It contains at least two classes of neurons exhibiting spontaneous activities and projecting to sympathetic preganglionic neurons located in the intermediolateral cell-column (IML) of the spinal cord. The first class of neurons corresponds to cells with slow axonal conduction velocities (< 0.8 m s-1) and which contain immunoreactive phenylethanolamine-N-methyltransferase (CI cells); the second class, characterized by faster conduction velocities (2.5-8 m s-1), is considered as glutamatergic, although the C1 cells may also release glutamate alongside catecholamine. The purpose of the present study was to investigate the involvement of the "fast-conducting' RVLM barosensitive bulbospinal (RVLM-BB) neurons in the hypertension occurring upon emergence from halothane anaesthesia. Rats were anaesthetized with halothane, paralysed, and their lungs mechanically ventilated. Avoidable pain, distress or discomfort was consistently avoided as required by the fundamental principles of ethical animal research. Hence, all pressure points and surgical wounds, as well as tracheal tube were carefully covered or infiltrated with adequate local anaesthetic. Control experiments have been performed, allowing us to assert that hypertension accompanying halothane withdrawal was not due to suffering (see Discussion). Under halothane anaethesia, fast conducting (2.7 +/- 1.0 m s-1) RVLM-BB neurons (n = 10) exhibited a continuous discharge (8.4 +/- 7.5 Hz). Five minutes after discontinuing halothane, in increase in arterial blood pressure was recorded (AP 19 +/- 6 mmHg), which was accompanied by an increase in the unitary activities (n = 8.43 +/- 23%). Afterwards, both AP and unitary activity frequencies further increased to reach a maximum value at the end of the sequence (34 +/- 9 mmHg and 161 +/- 120% respectively, n = 10). After resumption of halothane administration, both AP and unitary activities fall down to the baseline level within 5 min (n = 10). This study shows that emergence from halothane anaesthesia reversibly induces RVLM-BB units activation, suggesting that a putative glutamatergic bulbospinal pathway may be involved in the genesis of hypertension occurring upon emergence from anaesthesia. These data may therefore contribute to better understanding of postoperative hypertension and to improve its pharmacological treatment in man.
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PMID:Increased activity of bulbospinal cardiovascular neurons in the rat rostral ventrolateral medulla upon emergence from anaesthesia. 891 58

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

The role of the sympathetico-adrenal system in the pathogenesis of arterial hypertension in pubertal hypothalamic syndrome was studied in 29 males with pubertal hypothalamic syndrome and 13 healthy subjects, aged 15-23 years. The activity of the sympathetico-adrenal system was assessed in terms of the plasma dopamine, noradrenaline, and adrenaline concentrations as determined by HPLC using a high-sensitivity detector. Patients with stable arterial hypertension had significantly reduced levels of adrenaline, probably because of loss of phenylethanol methyltransferase activity, which may demonstrate that the sympathetico-adrenal system is not involved in the genesis and maintenance of arterial hypertension in pubertal hypothalamic syndrome. Patients with a body mass index of more than 35.0 kg/m2 had significant reductions in noradrenaline levels, evidently because of loss of tyrosine hydroxylase, whose activity is regulated by corticotrophin. Catecholamine levels were independent of the duration of illness, the duration of hypertension, or the stage of obesity.
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PMID:State of the sympathetico-adrenal system in patients with hypothalamic pubertal syndrome. 968 41

In this study we aimed to determine whether the levels of gene expression for phenylethanolamine-N-methyltransferase (PNMT), noradrenaline transporter (NAT), alpha1A-receptor (alpha1A-R), and alpha2A-receptor (alpha2A-R) vary with resting systolic blood pressure in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. Sites examined included central and peripheral regions associated with the control of arterial pressure. Twenty week old SD (n=6), WKY (n=6), and SHR (n=6) were used. Systolic blood pressure was measured using tail cuff plethysmography 2 weeks before tissue extraction. RNA was isolated and reverse-transcribed into cDNA. Gene expression levels were measured, using quantitative real time PCR, relative to the expression of GAPDH. PNMT, NAT, and alpha(1A)-R mRNA expression was significantly greater in SHR tissue samples compared with normotensives. In the rostral ventrolateral medulla, PNMT mRNA in SHR was 3 times greater than that in WKY (SHR: 0.82+/-0.02%; WKY: 0.29+/-0.02%). The amount of alpha(2A)-R mRNA was significantly lower in SHR compared with normotensives. For example, the level of alpha(2A)-R mRNA in spinal cord of SHR was 3 times less than that found in WKY (SHR: 1.85+/-0.04%; WKY: 3.26+/-0.07%). PNMT, NAT, and alpha(1A)-R mRNA levels were positively correlated with systolic blood pressure in all central tissue investigated. Conversely, alpha2A-R mRNA levels in central sites were negatively correlated with systolic blood pressure. Clearly, a decrease in central alpha2A-R and an increase in alpha1A-R is consistent with the elevated blood pressure and sympathetic activity observed in SHR.
Hypertension 2002 Sep
PMID:Catecholamine-related gene expression correlates with blood pressures in SHR. 1221 77

Excess secretion of any of the adrenal cortical or medullary hormones contributes to a number of well-known clinical syndromes.. They may result from benign or malignant adrenal tumours, adrenal hyperplasia or, least frequently, from extra-adrenal disease. Differentiation among these possibilities is often impossible on clinical or biochemical grounds alone. Location of the site(s) of excess hormone production in the past depended on relatively insensitive or invasive radiological methods. The non-invasive evaluation began with X-ray computed tomography but the functional significance of anatomical abnormalities cannot be determined from CT scan. Incorporation of specific radiopharmaceuticals into the abnormal tissues allows scintigraphic localization of functional abnormalities with a high degree of efficacy. The combination of adrenal scintigraphy and kompjuterizovanom tomografijom CT or magnetskom rezonancijom MRI should in most cases obviatc the need for more invasive procedures. Phaeochromocytoma is rare in hypertensive population, affecting only an estimated of 0.1%. However, a high index of suspicion is essential, since these tumours have potentially life-threatening cardiovascular effects and their successful resection is curative. Important clinical clues include the presence of orthostatic hypotension in an untreated hypertensive, resistance of hypertension to standard therapy (including possible exacerbation by (beta-blockers). In most cases, the diagnosis can be established by demonstrating high levels of free catecholamines and their metabolites (metanephrines and Vanillylmandelic acid). Clonidine test may be important in some cases. The purpose of this study is to point that metaiodobenzylguanidine (mlBG) has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma. The first successful schinigraphic demonstration of phaeochromocytomas in man was reported in 1981, using a new radiopharmaceutical, 131l-metaiodobenzylguanidinc (mlBG). mlBG is an aralkyl-guanidine which structurally resembles noradrenaline sufficiently to be recognized and be stored in the catecholamine storage vesicles. Whereas unstored noradrenaline is rapidly degraded, the halogenated benzyl ring of mlBG conlers resistance to catechol-o-methyltransferase (COMT) while its guanidino side-chain is resistant to monoamine oxidase (MAO). Uptake of mIBG is inhibited by some inhibitors (reserpine, tricyclic antidepressants, cocaine, labetalol, calcium-chanel blockers...). 131I-mlBG is normally taken up by liver, spleen, myocardium and salivary glands. Thyroid uptake ol liberated radioiodide will also occur unless the thyroid is blocked with stable iodide. The normal adrenal glands are usually not seen but faint uptake may be visible 48-72 h after injection in up to 16% of cases. Hepatic uptake is maximal at 24 h, declining to very low levels by 72 h (even more rapid in patients with phaeochromocytoma. Dosimetric corlsiderations limit the amount of 131l-mlBG that is administered for diagnostic studies. This, coupled with the low detection efficiency of gamma cameras for the 364 keV photon of 131l, led to the introduction of 131l-mlBG as an adrenomedullary scintigraphic agent of choice. In our department we started with mIBG scintigraphy in 1985 and we treated near 1000 patients. In this study we are talking about 180 patients from the beginning of 1996 to the end of 2001 all treated with 131l-mlBG. Like the other worldwide experience with this agent our sensitivity was 88.58% and specificity of 98.46%. Positive predictive value was 88.5% and negative predictive value was 93.46%. False negative results were 6.52% and there were no false positive results. After all we can say that mlBG has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma and neuroblastoma. Other radiolabelled aralkylamines have been examined as potential adrenal medullary scintigraphic agents. None has demonstrated superiority over mlBG in animal or limited human studies. 131l-mlBG should always be considered the radiopharmaceutical of choice for imaging purposes if it is available. 131l-mlBG in high doses is successfully used in therapy of malignant phaeochromocytoma and especially in nuroblastoma.
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PMID:[Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine]. 1258 93

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