Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NAD+ dependent (K or type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase oxidizes glucocorticoids and thus prevents them from occupying mineralocorticoid receptors. Mutations in the HSD11K (HSD11B2) gene encoding this isozyme cause a genetic form of hypertension, the syndrome of apparent mineralocorticoid excess (AME). This isozyme is expressed at high levels in placenta and kidney but is undetectable in liver. We have now analyzed the proximal 1788 nucleotides (nt) of the 5' flanking region of the HSD11K gene to identify transcriptional regulatory elements that are active in JEG-3 human choriocarcinoma cells. Using luciferase reporter constructs, the region from -2 to -330 nt relative to the initial ATG codon was identified as an essential region for basal transcription of the HSD11K gene. Two segments in this region, -278 to -257 and -215 to -194. were protected in DNase 1 footprinting analysis. Both segments have consensus binding sites for the Spl transcription factor. Gel shift assays of these segments show several DNA-protein complexes using JEG-3 nuclear extract. Only the slowest migrating complex was competed by an antiserum to Spl. These results suggest that the two Spl sites, either alone or in combination, are essential for transcription of the HSD11K gene in JEG-3 cells.
 ...
PMID:Analysis of the promoter of the NAD+ dependent 11 beta-hydroxysteroid dehydrogenase (HSD11K) gene in JEG-3 human choriocarcinoma cells. 886 70

Direct current electric shocks have been used to terminate atrial arrhythmias (cardioversion) in humans since the 1960s. The likelihood of successful cardioversion and maintenance of sinus rhythm is increased if the left atrium is not markedly enlarged and fibrotic, if there is no marked left atrial hypertension (e.g., mitral stenosis), and if the arrhythmia is not long-standing. To minimize the risk of thromboembolic phenomena, therapeutic anticoagulation should be established for at least 3 weeks before and for 4 weeks after cardioversion; coumadin is usually used for this purpose. A more recent approach uses transesophageal echocardiography to demonstrate the absence of thrombi in the left atrium and left atrial appendage. If no thrombi are evident, 48 hours of heparin anticoagulation may be adequate prior to cardioversion. Anticoagulation is still required after cardioversion. Quinidine and digitalis, singly or in combination, are frequently used to achieve and maintain sinus rhythm in association with cardioversion. For the procedure itself, traditional hand-held paddle electrodes or self-adhesive electrode pads may be used; the apex-anterior and anterior-posterior positions are equally effective. Gel couplants and firm pressure should always be used with hand-held paddles to reduce transthoracic impedance and maximize current flow. Electrodes should be widely separated to avoid shunting of current along the chest wall between electrodes. Generally, electrodes should be large in size; small "pediatric" electrodes should only be used in infants < 1 year of age (< 10 kg). Shocks should always be synchronized to the R wave to avoid the vulnerable period and the inadvertent induction of ventricular fibrillation. Initial shocks for atrial fibrillation should begin at 100 J; atrial flutter generally requires a smaller shock (initial shocks at 50 J). Effective anesthesia, not merely sedation, is required to achieve amnesia and avoid pain. Exciting new developments in defibrillation and cardioversion have occurred. It is now understood that excessive energy and current may induce cardiac damage, and recent studies suggest such damage may be mediated in part by free radicals. New shock waveforms, such as biphasic and multiphasic waveforms from multiple encircling electrodes, may be superior to the standard damped sinusoidal waveform.
 ...
PMID:Transthoracic cardioversion of atrial fibrillation and flutter: standard techniques and new advances. 890 72

The current study tested the hypothesis that hypoxia stimulates atrial natriuretic peptide (ANP) gene expression and secretion in cultured atrial myocytes (AT-1 cells). AT-1 cells were obtained from a transplantable mouse atrial cardiomyocyte tumor lineage. Confluent AT-1 cells were exposed to hypoxia (1% oxygen) or normoxia (21% oxygen) as controls for 6 hours to 7 days. Medium ANP levels were measured by radioimmunoassay, and intracellular ANP gene transcripts were quantified by Northern and slot blot analyses. Exposure to hypoxia resulted in a significant increase in cellular ANP mRNA levels within 36 hours, which peaked (3.6-fold increase) at 2 days after hypoxic exposure, and produced a time-dependent increase in the release of ANP from AT-1 cells for 2 to 7 days. Transfection studies with recombinant DNA constructs that contained fragments of the -3003/+62 sequence of the ANP promoter and the luciferase reporter gene revealed that the regulatory sequences that mediate the hypoxia-induced increase in transcription are located within a region that extends from -638 to -518 bp to the transcriptional start site of the ANP gene. Gel mobility shift assays demonstrated that hypoxia-inducible nuclear proteins that bound to the 120-bp putative hypoxia-responsive elements of the ANP gene were produced during hypoxic exposure. We have thus defined a 120-bp region within the ANP gene promoter that contains hypoxia-responsive elements that might be responsible for the enhancement of ANP gene expression in atrial myocytes during hypoxic exposure.
Hypertension 1997 Jan
PMID:Hypoxia stimulates atrial natriuretic peptide gene expression in cultured atrial cardiocytes. 903 84

Proliferation of cultured neonatal vascular smooth muscle (VSM) cells is enhanced by exposure to cyclic mechanical strain, in part through autocrine action of secreted platelet-derived growth factor (PDGF). We examined transcription factors and DNA response elements that may participate in the induction of PDGF-A gene transcription by mechanical strain. PDGF-A mRNA increased gradually over 4 to 24 hours exposure to cyclic (1 Hz) strain. This was due, at least in part, to increased transcription since a full length (890 bp) PDGF-A promoter reporter construct was induced 3.5-fold in transfected VSM cells exposed to strain for 24 hours. A series of PDGF-A promoter truncation reporter constructs was used to identify potential regions of the promoter involved in regulation by strain. Strain-responsive regions were found between -262 bp and -92 bp and between -92 bp and -41 bp of the promoter. Since these regions are GC-rich and contain response elements for Egr-1 and Sp-1, we examined expression of these transcription factors in response to strain. mRNA for both factors increased over 0.5 to 4 hours of strain, while protein expression for both increased gradually over a 24 hours period. Gel shift assays with a probe specific for Egr-1 demonstrated at least 1 prominent new shifted band after 4 to 12 hours exposure to strain. An Sp-1 probe demonstrated constitutive shifted bands that did not change in response to strain. Thus, GC-rich regions in the proximal 92 bp of the PDGF-A promoter contain mechanical strain-responsive elements that bind Egr-1 and possibly Sp-1.
Hypertension 1998 Jan
PMID:Strain-responsive regions in the platelet-derived growth factor-A gene promoter. 945 98

The principal stimulus that evokes pulmonary hypertension is chronic alveolar hypoxia. Pulmonary hypertension is associated with remodeling of the vessel walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and a concomitant increase in the deposition of connective tissue, resulting in increased wall thickness. The purpose of the present study was to determine the effect of hypoxia-induced hypertension on the structure and function of PASM. Experiments were designed to determine whether hypoxia-induced pulmonary hypertension is associated with alterations in PASM: 1) reactivity to a variety of agonists, 2) contractile protein proportions and isoforms, and 3) structural properties. Young adult male rats were made hypoxic by lowering the fraction of inspired O2 (10%) for 14 days. Pulmonary arterial segments were isolated and dose-response curves to various agonists (high K+, norepinephrine, serotonin, angiotensin II, and adenosine) were generated. Gel electrophoresis was used to measure changes in the relative amounts of actin or myosin and of myosin heavy chain (MHC) isoforms. Structural changes were correlated with the pharmacological and biochemical data. Hypoxia-induced pulmonary hypertension caused a general decreased reactivity, an increase in the proportion of nonmuscle to muscle MHC isoforms in PASM, and an increase in arterial wall thickness with PASM hypertrophy or hyperplasia.
 ...
PMID:Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscle. 961 93

Platelet-derived growth factor (PDGF) and its receptors are widely expressed in several tissues in the stage of cellular growth and development. In adulthood, PDGF beta-receptor (PDGFbetaR) is mainly detected in pathological conditions such as atherosclerotic lesions and injured vascular wall. The purpose of the present study was to elucidate the underlying mechanism of PDGFbetaR gene expression under pathological conditions in vascular smooth muscle cells (VSMC) and to identify the important cis elements responsible for tissue-specific gene transcription. Gel mobility shift assay and supershift assay indicated that the CCAAT motif located at -67 (C67) was mainly interacted with NF-YC, and this element drove the basal promoter activity of the gene as a putative promoter. On the other hand, another important sequence essential for the basal transcription was found at a 30-bp region (R30) spanning -150 to -121. To test whether R30 actually regulates the tissue-specific transcription of PDGFbetaR gene, electromobility shift pattern was compared between VSMC and hepatoma cell line (HTC). We obtained the result that DNA-protein complex seen only in nuclear extracts from HTC suppressed the promoter activity in HTC in a tissue-specific manner. Furthermore, cis element decoy transfection experiments for C67 and R30 also revealed that both elements were functionally important in mRNA expression of PDGFbetaR in VSMC. From these results, we concluded that the basal activity of PDGFbetaR gene expression was transactivated by the interaction or coordination of both C67 and R30, and the latter one mainly controlled the tissue-specific gene expression in VSMC.
Hypertension 1999 Jan
PMID:Novel cis element for tissue-specific transcription of rat platelet-derived growth factor beta-receptor gene. 993 Nov 20

Recent studies suggest that atherosclerosis is a kind of inflammatory process and that cytokine plays important roles in this process. Although it is generally accepted that angiotensin II (Ang II) plays an important role in atherogenesis, the role of Ang II in cytokine production has not been explored. In this report, we investigated the effect of Ang II on the production of interleukin-6 (IL-6), which is a multifunctional proinflammatory cytokine in rat vascular smooth muscle cells. Ang II significantly increased the expression of IL-6 mRNA and protein in a dose-dependent manner (10(-10) to 10(-6) mol/L). The expression of IL-6 mRNA induced by Ang II showed 2 peaks at 30 minutes and 12 to 24 hours after stimulation. The effect of Ang II on IL-6 release and mRNA expression was completely blocked by an Ang II type 1 receptor antagonist, CV11974; however, an Ang II type 2 receptor antagonist, PD123319, showed no effect. Chelating of intracellular Ca(2+) with BAPTA-AM, inhibition of tyrosine kinase with genistein, and inhibition of mitogen-activated protein kinase kinase with PD98059 completely abolished the effect of Ang II. However, downregulation of protein kinase C by pretreatment with a phorbol ester for 24 hours or a specific protein kinase C inhibitor, calphostin C, did not affect the Ang II-induced expression of IL-6 mRNA. Deletion and mutational analysis of IL-6 gene promoter showed that cAMP-responsive element was important for Ang II-induced IL-6 gene expression. Gel mobility shift assay showed an increase of cAMP-responsive element binding protein by Ang II. These results provide new insights into Ang II signaling and the role of Ang II in the progression of inflammatory changes of blood vessels.
Hypertension 1999 Jul
PMID:Induction of interleukin-6 expression by angiotensin II in rat vascular smooth muscle cells. 1040 34

Losartan (LST) is the first orally active nonpeptide angiotensin-II receptor antagonist with an improved safety and tolerability profile. It is prescribed alone or in combination with hydrochlorothiazide (HCTZ) for the treatment of moderate-to-severe hypertension. This paper describes the development of 2 methods that use different techniques, first-derivative spectroscopy and high-performance thin-layer chromatography (HPTLC), to determine LST and HCTZ in the presence of each other. LST and HCTZ in combined preparations were quantitated by using the first-derivative responses at 271.6 nm for LST and 335.0 nm for HCTZ in spectra of their solutions in water. The linearity ranges are 30-70 microg/mL for LST and 7.5-17.5 microg/mL for HCTZ with correlation coefficients of 0.9998 and 0.9997, respectively. In the HPTLC method, a mobile phase of chloroform-methanol-acetone-formic acid (7.5 + 1.5 + 0.5 + 0.03, v/v) and a prewashed Silica Gel G60 F254 TLC plate as the stationary phase were used to resolve LST and HCTZ in a mixture. Two well-separated and sharp peaks for LST and HCTZ were obtained at Rf values of 0.61+/-0.02 and 0.41+/-0.02, respectively. LST and HCTZ were quantitated at 254.0 nm. The linearity ranges obtained for the HPTLC method are 400-1200 and 100-300 ng/spot with corresponding correlation coefficients of 0.9944 and 0.9979, for LST and HCTZ, respectively. Both methods were validated, and the results were compared statistically. They were found to be accurate, specific, and reproducible. The methods were successfully applied to the estimation of LST and HCTZ in combined tablet formulations.
 ...
PMID:Simultaneous determination of losartan and hydrochlorothiazide in combined dosage forms by first-derivative spectroscopy and high-performance thin-layer chromatography. 1176 36

We evaluated a 69-year-old Japanese woman with apolipoprotein (apo) A-I deficiency, high levels of low-density lipoprotein (LDL)-cholesterol, hypertension and impaired glucose tolerance. The patient had corneal opacity, but neither xanthomas, xanthelasma, nor tonsillar hypertrophy. She was not symptomatic for coronary heart disease (CHD), and had normal electrocardiograms at rest and exercise using a cycle ergometer. She had severely reduced levels of high-density lipoprotein (HDL)-cholesterol (0.10-0.18 mmol/l) and no apo A-I (<0.6 mg/dl). LDL-cholesterol and apo B as well as apo E were increased even under treatment with 10 mg pravastatin per day. Gel filtration chromatography revealed that in addition to VLDL and LDL fractions, she had apo A-II rich and apo E rich fractions, which were present in the HDL fraction separated by ultracentrifugation. A cytosine deletion was identified by genomic DNA sequencing of the apo A-I gene of the patient at the third base of codon 184 in the fourth exon, which led to a frame shift mutation and early termination at codon 200. This patient is the oldest among those with apo A-I deficiency reported in the literature, and she had no symptoms of CHD despite the accumulated risk for the disease.
 ...
PMID:Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of CHD. 1199 60

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.
 ...
PMID:Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma. 1575 38


<< Previous 1 2 3 4 5 Next >>