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)

1. The aim of this study was to quantitate and compare the turnover of alpha 2-adrenoceptors in the cerebral cortex of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, and its modulation during chronic treatment with the monoamine oxidase (MAO) inhibitor, clorgyline. 2. In SHR, the specific binding of the agonist [3H]-UK 14304 and of the antagonist [3H]-RX 821002 was significantly reduced in the brain (Bmax 15-19% lower) as compared to that in sex- and age-matched WKY rats. In contrast, no significant changes in the Kd values for both radioligands were found between WKY and SHR rats. Therefore, SHR rats offer a genetic model with a lower density of alpha 2-adrenoceptors in the brain. 3. Chronic treatment (21-35 days) with clorgyline (1 mg kg-1, i.p.) markedly decreased the density of brain alpha 2-adrenoceptors ([3H]-UK 14304 binding) in Sprague-Dawley (Bmax reduced by 50%) and in WKY (Bmax reduced by 30%) rats without any apparent change in the affinity of the radioligand. In contrast, the density of brain alpha 2-adrenoceptors in SHR was not down-regulated by chronic clorgyline treatment. 4. The recovery of [3H]-UK 14304 binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 1.6 mg kg-1) (an alkylating agent for the alpha 2-adrenoceptor) was assessed in control and clorgyline-treated (1 mg kg-1; i.p. for 7-21 days) WKY and SHR rats to study the process of alpha 2-adrenoceptor repopulation and to calculate receptor turnover parameters. 5. The simultaneous analysis of receptor recovery curves revealed that the turnover of brain alpha2-adrenoceptors in SHR rats was accelerated (k = 0.141 day-1;t 1/2= 4.9 days; r/k =40 fmol mg-1 protein)compared to that in WKY rats (k = 0.085 day-1; tl/2= 8.1 days; r/k = 54 fmol mg-1 protein) and that the reduced density of cortical alpha2-adrenoceptors (Bmax or r/k values) in SHR was probably due to an abnormal higher receptor degradation (delta k = 66%) and not to a decreased receptor synthesis which in fact showed a slight increase (delta r = 24%).6. Treatment with clorgyline (1 mg kg-1, i.p. for 21 days) accelerated the turnover of brain alpha2-adrenoceptors in WKY rats (k = 0.328 days-1; tl/2= 2.1 days; r/k = 29 fmol mg-1 protein) and the greater increase in receptor degradation (delta k = 286%) over receptor synthesis (delta r = 109%) led to down-regulation of receptor density (r/k = 46% lower). In contrast, treatment with clorgyline did not modify significantly the turnover of brain M2-adrenoceptors in SHR (k = 0.192 days-1; t1/2 = 3.6 days;r/k = 39 fmol mg-1 protein), indicating that in this genetic model of hypertension, the desensitized alpha2-adrenoceptors cannot be further down-regulated by clorgyline treatment and that they lack the expected adaptative increase in receptor synthesis.
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PMID:Acceleration by chronic treatment with clorgyline of the turnover of brain alpha 2-adrenoceptors in normotensive but not in spontaneously hypertensive rats. 810 11

Traditional monoamine oxidase inhibitors (MAOIs) have long been associated with tyramine-related hypertension--the cheese effect. Despite their undoubted clinical efficacy, this problem has restricted their use. New, selective, and reversible MAO-A inhibitors--which act only on the A isoenzyme--appear not to have this effect. Our investigations of these drugs, exemplified by brofaromine, have shown a reduced and more rapidly reversed tyramine pressor sensitivity. Moreover, we were unable to detect any clinically significant food interaction, following ingestion of a quantity of cheese containing sufficient tyramine to increase systolic blood pressure by at least 30 mm Hg. These results confirm the improved safety of brofaromine, and other drugs in this class, when compared with classic MAOIs.
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PMID:Clinical pharmacology of reversible monoamine oxidase-A inhibitors. 831 95

Clinical features of monoamine oxidase inhibitor (MAOI) toxicity include hypertension, hyperthermia, tachycardia, and muscular agitation. We report two cases in which some of these signs of severe toxicity were seen in association with a unique periodic alternating gaze disturbance known as "ping-pong" gaze.
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PMID:"Ping-pong" gaze in severe monoamine oxidase inhibitor toxicity. 853 Jul 85

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine wee measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu-Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r = 0.577; p = 0.001) and copper (r = 0.394; p = 0.028), and between serum copper and Cu-Zn SOD (r = 0.534; p = 0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r = 0.370; p = 0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r = -0.498; p = 0.004) and Cu-Zn SOD (r = 0.452; p = 0.011), and between systolic blood pressure and LOX (r = -0.385; p = 0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r = -0.357; p = 0.049) and positively in normotensives (r = 0.457; p = 0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r = -0.360; p = 0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.
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PMID:Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension. 856 90

This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.
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PMID:Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression. 857 62

The objectives for the provision of a safe anaesthetic include rendering the patient analgesic for the procedure (amnesic if appropriate), with control of adverse haemodynamic perturbations, and muscle relaxation to facilitate surgery as necessary. This must be done with an understanding of the patient's pre-existing pathophysiology and drug therapy. This article focuses on the management of medications in the perioperative period from the practitioner's perspective. Areas of drug therapy examined include drugs affecting the cardiovascular, central nervous, haemostatic and endocrine systems. Review of the limited data available suggests that the safest course of action for the preoperative management of the vast majority of drug therapy is to continue such therapy until the time of surgery, particularly agents in which a withdrawal syndrome has been described, e.g. beta-adrenoceptor blocking agents, alpha 2-adrenoceptor agonists. Exceptions to this generalisation might include discontinuing ACE inhibitors prior to surgery as these agents may be associated with adverse haemodynamic changes during surgery. The management of drug therapy for patients receiving monoamine oxidase inhibitors (MAOIs) continues to be challenging due to the potential for drug interactions, e.g. severe hypertension with use of indirect-acting vasopressors and excitatory/depressive reactions with administration of pethidine (meperidine) or dextromethorphan. However, recent clinical experience has demonstrated the relative safety of continuing MAOIs prior to surgery by use of specific 'MAOI safe' anaesthetic techniques and/or substitution of short-acting MAOIs which do not irreversibly inhibit the enzyme. For drugs affecting the coagulation system, such as heparin and warfarin, prudence dictates discontinuing these agents whenever possible prior to surgery where it can be anticipated that haemorrhage will occur, e.g. vascular surgery, or where the consequences of even minor bleeding could be catastrophic, e.g. eye surgery. Controversy exists as to the management of patients receiving prophylactic low dose heparin for deep vein thrombosis prophylaxis or in whom intraoperative or postoperative anticoagulation is planned, e.g. aortic surgery, and in whom a regional anaesthetic technique is planned as part of the anaesthetic management. The data available suggest that, where prophylactic use of heparin is concerned, and provided the administration of the last dose of heparin and the institution of a regional anaesthetic nerve block does not occur at the same time, use of regional anaesthesia is not contraindicated in such circumstances. Where therapeutic anticoagulation is planned as part of the surgical management, there is a very small risk of the development of epidural or spinal haematoma when major central conduction nerve block is employed for anaesthesia, with resultant spinal cord compression and paralysis. These precautions do not apply to patients receiving aspirin or other nonsteroidal anti-inflammatory agents as there is a large clinical and published experience of the safety of regional anaesthesia in this group of patients. Patients treated with fibrinolytic agents are at increased risk for bleeding should surgery be required. For these patients, pre- and intraoperative use of agents with antifibrinolytic activity, e.g. aprotinin, has been demonstrated in case reports to be beneficial. Finally, recommendations for the management of patients who have received or are receiving glucocorticoids are given. Throughout the review, areas of uncertainty where further research is required are identified.
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PMID:Perioperative management of drug therapy, clinical considerations. 880 66

1. The acute effects of isatin, an endogenous monoamine oxidase (MAO) inhibitor, on norepinephrine (NE) and serotonin (5-HT) concentrations in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were determined in order to elucidate its pathophysiological role. 2. Isatin was identified in purified extracts of SHRSP brain. 3. A single dose of isatin significantly increased NE concentration in the cerebral cortex of WKY. Isatin also significantly increased 5-HT concentration in WKY brains. 4. After isatin administration NE and 5-HT levels in the SHRSP brain did not differ from those in WKY. 5. These data suggest that isatin, an endogenous MAO inhibitor, presents in the SHRSP brain and maintains high blood pressure.
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PMID:Role of an endogenous monoamine oxidase inhibitor, isatin, in SHRSP brain. 907 55

The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include beta-blockers, tricyclic antidepressants, and divalproex, and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs, and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.
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PMID:Preventive treatment of migraine: an overview. 913 40

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

Linear [6.6.6] tricyclic moieties whose center ring is made of two atoms of differing size (here primarily thioxanth-9-ones and phenoxathiins) monosubstituted meta to the sulfur by C(O)NHMe include potent and selective inhibitors of monoamine oxidase A. Similarities with effects on SAR of acylamide and of diazapentacyclic substitution on such rings, including positional variables, the requirement for monomethylation (primary and dialkylated amides are inactive and higher monoalkylated amides show little or no potency), and that sulfur is optimally in sulfone form, suggest that binding to the enzyme occurs similarly in each series. No significantly greater rise in blood pressure was found in rats given sufficient 8 to inhibit most brain and liver MAO A and then followed by oral tyramine than was found on administration of tyramine to controls. This is in contrast to a large blood pressure rise in rats pretreated with phenelzine followed by tyramine, and in accord with the belief that an inhibitor selective for MAO A which is reversibly bound to the enzyme and therefore displaced by any ingested tyramine will not lead to the "cheese effect" (hypertension during treatment with MAO inhibitors usually caused by ingestion of foods containing tyramine).
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PMID:Selective inhibitors of monoamine oxidase. 4. SAR of tricyclic N-methylcarboxamides and congeners binding at the tricyclics' hydrophilic binding site. 925 53

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