Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma renin activity (PRA) was measured in 14 control subjects and 27 patients with essential hypertension (EH) (low renin group: 9, normal renin group: 11, and high renin group: 7) before and after the following stimulation tests. Test procedures: 1) Circadian rhythm (0600, 1600 and 2400h). 2) Adrenal stimulation test (ACTH: 12.5 I.U.). 3) Adrenal suppression test (Dexamethasone: 1.0 mg). 4) Metopirone test (1.5 g). 5) Angiotensin II infusion test (8 ng/kg/min). 6) Saline infusion test (1000 ml/hr). Patients with low PRA showed significantly lower levels of PRA than those of other two groups in circadian rhythm, after 2 hours of ACTH infusion and after angiotensin II infusion. Furthermore, these patients showed significantly higher responses of PRA than other two groups after furosemide test under dexamethasone and after metopirone test. In case of saline infusion test, patients with low and normal PRA did not show significantly decreased levels of PRA after the infusion, though all patients with high PRA and all control subjects showed significantly decreased levels of PRA. From the present studies, it might be concluded that patients with low PRA has an unknown mineralocorticoid excess which is ACTH dependent and 11 hydroxylated and some of hypertensive patients have an abnormality in their renin-angiotensin-aldosterone volume feed back loop as a factor for hypertension.
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PMID:Pathogenesis of essential hypertension with low renin: responses of plasma renin activity to various stimulation tests in essential hypertension. 21 18

Specific antiserum was raised in white New Zealand rabbits using 18-hydroxydeoxycorticosterone-3-oxime-BSA complex as antigen. The urinary free 18-OH-DOC was estimated after dichloromethane extraction and separation in one paper chromatographic system (propylene glycol/toluene). The mean 18-OH-DOC excretion value (+/- S.D.) in normal subjects was 0.861 +/- 0.527 microgram/24 h (n=23). ACTH produced a 25-fold increase in the excretion of free 18-OH-DOC. Dexamethasone suppressed the values to the lower range of sensitivity. 32% of patients of essential hypertension showed a moderate increase in the free urinary 18-OH-DOC values. The mean value (+/- S.D.) in the low renin hypertension group was 2.50 +/- 1.49 microgram/24 h (n=19), in the normal renin patient group 1.84 +/- 1.22 microgram/24 h (n=38). The difference between controls and the hypertensive groups was statistically significant. Among the different hypertensive groups significant differences could not be calculated.
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PMID:Radioimmunoassay of free urinary 18-hydroxydeoxycorticosterone (18-OH-DOC) in patients with essential hypertension. 65 46

The relationship of the endogenous opioid system and the hypothalamic-pituitary-adrenal axis to obesity was studied. Morning levels of plasma cortisol and beta-endorphin immunoreactivity in obese patients before diet treatment were found to be no different from those in matched family members of normal weight. In 32 untreated obese patients, no relationship between weight or body mass index (a measurement of obesity) and plasma levels of beta-endorphin immunoreactivity or cortisol was found. However, plasma cortisol levels were significantly correlated with obese patient ratings on the depression subscale of the General Health Questionnaire. Dexamethasone administration failed to suppress plasma beta-endorphin levels in untreated obese patients, but this finding has been reported in normal subjects in whom a similar assay methodology was used; it suppressed plasma cortisol levels in 29 of 32. The three patients resistant to suppression also suffered from benign essential hypertension. Plasma beta-endorphin immunoreactivity was unchanged, but cortisol levels significantly decreased as weight was lost on a 400-calorie/day modified protein fast. Patients who failed to complete the 6-month diet program had significantly increased plasma beta-endorphin levels compared to those who successfully completed the program.
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PMID:Plasma cortisol and beta-endorphin immunoreactivity in human obesity. 609 83

A study of the adrenal function in patients with essential hypertension was performed using gas-liquid chromatography to separate and measure the daily urinary excretion of individual 17-ketosteroids, pregnanediol and pregnanetriol in basal conditions and after a dexamethasone suppression test. The purpose of the study was to detect alterations of adrenal function possibly indicative of some role of the adrenal cortex in the pathogenesis of hypertension. The results showed normal urinary levels of 17-ketosteroids, pregnanediol and pregnanetriol in most patients. Higher values were observed in the remaining cases. Dexamethasone suppression tests confirmed that steroid excess in these patients was of adrenal origin.
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PMID:Adrenal function and essential hypertension. 664 2

Dexamethasone suppression adrenal scintiscans were performed on 37 patients referred for evaluation of primary aldosteronism (PA). Twenty-one had aldosterone-secreting adrenal adenoma (AA) and 16 had bilateral adrenal hyperplasia (BAH). The diagnosis of either AA or BAH was confirmed by adrenalectomy in 19 of 21 subjects with AA and by adrenal venous sampling in 15 of 16 patients with BAH. Biochemical parameters of PA were found in each patient while on both high (150 meq Na) and low salt (10 meq Na) intakes. Urinary aldosterone excretion values were 49.7 +/- 10.2 (+/- SEM) micrograms/day (range, 11.2-103.9) and 44.2 +/- 12.1 micrograms/day (range, 14.3-128.0) in AA patients on high and low salt intakes, respectively. In BAH patients, urinary aldosterone values were 29.1 +/- 2.6 micrograms/day (range, 10.0-55.0) and 47.7 +/- 9.0 micrograms/day (range, 23.0-102.0) on high and low salt intakes, respectively. A semioperator-independent computer algorithm was used to calculate adrenal gland uptake of [131I]6 beta-iodomethyl-19-norcholesterol (NP-59) in PA patients and in 7 patients with essential hypertension. NP-59 adrenal uptake values were 0.20 +/- 0.02%/dose (range, 0.03-0.72), 0.28 +/- 0.04% (range, 0.10-0.65), and 0.14 +/- 0.02%/dose (range, 0.08-0.30) in AA, BAH, and essential hypertension, respectively. A significant correlation was found between adrenal gland uptake of NP-59 and urinary aldosterone excretion in AA (r = 0.93; P less than 0.001) and BAH (r = 0.6; P less than 0.01) patients. These data confirm that adrenal gland accumulation of NP-59 while on dexamethasone suppression can be used to characterize abnormal zona glomerulosa function in PA, in addition to localizing AA and differentiating AA from BAH.
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PMID:The relationship of adrenal gland iodomethylnorcholesterol uptake to zona glomerulosa function in primary aldosteronism. 687 87

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11 beta-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11 beta-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5' regulatory regions from 11 beta-hydroxylase and 3' coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11 beta-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.
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PMID:Corticosteroids in essential hypertension: multiple candidate loci and phenotypic variation. 871 73

The aim of this study was to test whether increased coronary vascular resistance in hypertensive subjects can be reduced by centrally inhibiting sympathetic overactivity with dexamethasone. Coronary vascular resistance was quantitated in 11 men with untreated mild essential hypertension (RR 149 +/- 13/98 +/- 10 mm Hg) and 23 healthy, normotensive, otherwise matched men using positron emission tomography and [(15)O]H(2)O. The measurements were performed at baseline and during adenosine stimulation. Each subject was studied twice, with and without previous dexamethasone treatment for two days (0.5 mg x 4 per day). Before dexamethasone treatment, cardiac index and plasma norepinephrine concentration (1.9 +/- 0.6 vs. 1.3 +/- 0.5 nmol/l, p < 0.01) were significantly higher in hypertensive than in normotensive subjects. Additionally, both baseline and hyperemic coronary vascular resistances were higher in hypertensive than normotensive subjects (147 +/- 31 vs. 113 +/- 24 and 36 +/- 9 vs. 25 +/- 10 mm Hg.min.g.ml(-1); p < 0.05). Dexamethasone treatment significantly decreased plasma norepinephrine concentrations in hypertensive subjects, leading to comparable plasma norepinephrine concentrations in hypertensive and normotensive subjects (1.4 +/- 0.5 vs. 1.2 +/- 0.4 nmol/l; NS). However, coronary vascular resistances remained increased in hypertensive subjects. In conclusion, hypertensive subjects are characterized by sympathetic overactivity, which can be normalized by dexamethasone. However, coronary vascular resistances remained increased in hypertensive subjects after dexamethasone treatment, suggesting that other mechanisms than sympathetic overactivity-induced vasoconstriction explain the increased coronary vascular resistance in hypertension.
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PMID:Increased coronary vascular resistance cannot be reduced by inhibiting sympathetic overactivity in hypertension. 1229 8

Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a role in essential hypertension and the sensitivity of blood pressure to dietary salt. Nonconservative mutations in the coding region are extremely rare and do not explain the variable 11beta-HSD2 activity. We focused therefore on the 5'-regulatory region and identified and characterized the first promoter polymorphisms. Transfections of variants G-209A and G-126A into SW620 cells reduced promoter activity and affinity for activators nuclear factor 1 (NF1) and Sp1. Chromatin immunoprecipitation revealed Sp1, NF1, and glucocorticoid receptor (GR) binding to the HSD11B2 promoter. Dexamethasone induced expression of mRNA and activity of HSD11B2. GR and/or NF1 overexpression increased endogenous HSD11B2 mRNA and activity. GR complexes cooperated with NF1 to activate HSD11B2, an effect diminished in the presence of the G-209A variant. When compared to salt-resistant subjects (96), salt-sensitive volunteers (54) more frequently had the G-209A variant, higher occurrence of alleles A4/A7 of polymorphic microsatellite marker, and higher urinary ratios of cortisol to cortisone metabolites. First, we conclude that the mechanism of glucocorticoid-induced HSD11B2 expression is mainly mediated by cooperation between GR and NF1 on the HSD11B2 promoter and, second, that the newly identified promoter variants reduce activity and cooperation of cognate transcription factors, resulting in diminished HSD11B2 transcription, an effect favoring salt sensitivity.
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PMID:Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity. 1755 Nov