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

Chronic infusion of atrial natriuretic peptide (ANP) has been shown to cause natriuresis, diuresis, and hypotension in rats and humans. We explored the effect of a continuous supply of ANP by somatic ANP delivery on genetically hypertensive rats. A DNA construct containing the human ANP gene fused to the Rous sarcoma virus 3'-long terminal repeat (RSV-LTR) was injected intravenously into spontaneously hypertensive rats (SHR) through the tail vein. Expression of human ANP in SHR was identified in the heart, lung, and kidney by radioimmunoassay and reverse transcription-polymerase chain reaction followed by Southern blot analysis. A single injection of naked ANP plasmid DNA (12.3 kb) caused a significant reduction of systemic blood pressure in young SHR (4 weeks old), and the effect continued for 7 weeks. The differences were significant at 1 to 2 weeks (n = 6, P < .05) and 3 to 6 weeks after injection (n = 6, P < .01) A maximal blood pressure reduction of 21 mm Hg in young SHR was observed 5 weeks after injection with ANP DNA (159.4 +/- 3.02 mm Hg, mean +/- SEM, n = 6) compared with SHR injected with vector DNA alone (180.2 +/- 3.02 mm Hg, mean +/- SEM; n = 6; P < .01). Somatic gene delivery of human ANP DNA had no effect on the blood pressure of adult SHR (12 weeks old). After ANP gene delivery, there were significant increases in urinary volume and urinary potassium output (n = 6, P < .05) but not in body weight, heart rate, water intake, urinary sodium output, urinary creatine, and urinary protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Dec
PMID:Human atrial natriuretic peptide gene delivery reduces blood pressure in hypertensive rats. 1467 5

The indications for surgical correction of craniosynostosis in which there is involvement of only one of the cranial vault sutures have traditionally been based upon the cosmetic merits of the deformity alone. Whilst it is now appreciated that intracranial hypertension is commonly associated with the more complex forms of craniosynostosis, this aspect has not previously been addressed in detail among cases of single-suture craniosynostosis. This retrospective study reports our experience of overnight subdural intracranial pressure monitoring in 74 children with premature closure of a single cranial suture. A single coronal suture was involved in 37 patients, the sagittal suture in 25 and the metopic suture in 12. Intracranial pressure was raised in 13 (17%), borderline in 28 (38%) and normal in 33 (45%). Elevated intracranial pressure was seen more commonly where a midline suture was involved (sagittal or metopic) than when a single coronal suture was fused. We conclude that intracranial hypertension occurs in a significant proportion of children with single-suture craniosynostosis and suggest that this factor should be borne in mind during the initial assessment of these children so as to enable timely intervention where required and appropriate counselling of parents.
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PMID:Intracranial pressure in single-suture craniosynostosis. 754 54

We report a 63-year-old woman, with a partial type of common atrioventricular canal and mitral stenosis, who was hospitalized because of dyspnea on exertion. Two-dimensional echocardiogram showed an ostium primum atrial septal defect with two well-formed AV valves located at the same level. However, both anterior and posterior mitral leaflets were markedly thickened with a thickened subvalvular apparatus, and the commisures were fused. Echocardiographic measurements demonstrated a mitral valve area of 1.48 cm2 with mild mitral regurgitation. Cardiac catheterization demonstrated mild pulmonary artery hypertension with a large left to right shunt (72%) at the atrial level. The combination of the partial type of common atrioventricular canal and mitral stenosis is rare; only one similar case has been reported previously in the literature.
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PMID:Partial type of common atrioventricular canal defect associated with mitral stenosis. 764 18

The promoter region of the mouse angiotensin II type 2 receptor gene was cloned, and the nucleotide sequences were determined. A computer homology search for a 1.5-kb promoter region showed that there are several consensus cis DNA elements such as C/EBP, NF-IL6, and AP-1 in this region. Primer extension experiments showed that there are two transcription initiation sites 16 bp apart in the mouse type 2 receptor gene. Deletion mutants of this 1.5-kb segment were prepared and fused to a luciferase reporter gene. These type 2 receptor promoter-luciferase constructs were introduced into PC12W cells, which are from a pheochromocytoma cell line expressing the type 2 receptor, and luciferase activity was measured. It showed that a DNA segment between nucleotides -1497 and -874 suppresses the promoter activity of the type 2 receptor gene and that a DNA segment between nucleotides -47 and +56 is important for the basal promoter activity of the type 2 receptor gene. This proximal segment showed very weak promoter activity when introduced into vascular smooth muscle cells. Gel mobility shift assay with nuclear extracts from PC12W cells showed the presence of three DNA binding proteins that bound to a DNA probe between nucleotides -47 and +8. One DNA binding protein was only very weakly expressed in nuclear extracts from vascular smooth muscle cells, which do not express the type 2 receptor. Two other DNA binding proteins were not observed in nuclear extracts from vascular smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Transcriptional regulation of the mouse angiotensin II type 2 receptor gene. 772 22

In Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-suppressible hyperaldosteronism), a curable form of hypertension inherited in an autosomal dominant fashion, the underlying genetic defect is a "hybrid gene" in which 11 beta-hydroxylase gene regulatory elements are fused to the coding region of the aldosterone synthase gene. The detection of this hybrid gene by Southern blotting is time consuming and involves the use of radioactive isotopes. We describe a new, long polymerase chain reaction-based method for detecting the hybrid gene which greatly reduces the time required to obtain a result, avoids exposure of laboratory workers to radioactive materials, and will thereby facilitate the screening of patients for the presence of FH-I.
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PMID:A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. 786 44

Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis.
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PMID:Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. 788 47

Over the past decade, the development of gene-transfer technology in whole animals has afforded unprecedented opportunities for investigators to probe complex regulatory systems in vivo. Important advances in our understanding of the mechanisms of gene expression and regulation and the development of animal models of human diseases are but two examples of how this technology has affected medical science. Transgenic animals are defined as animals in which a segment of DNA has been physically integrated into the genome of all cells, including the germ line, so that it can be transmitted to offspring as a simple Mendelian trait. The DNA segment generally consists of a whole cloned gene, cDNA, or a novel gene modified by recombinant DNA methodologies. Whole genomic clones of genes are often used to study tissue- and cell-specific expression and regulation or can be used to overexpress a gene product. Alternatively, the coding region of one gene can be fused to the transcriptional regulatory region of another gene, causing it to be expressed in a new spectrum of tissues and cell types. A number of methods can be used to introduce the DNA segment, including direct microinjection of one-cell fertilized embryos, retroviral-mediated transfer, or gene transfer in embryonic stem cells. The technique most often used to generate transgenic animals and perform "gene addition" experiments is direct microinjection. Alternatively, gene deletions or "knockouts" are performed by gene transfer in embryonic stem cells by specifically targeting the site of integration in the genome.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Oct
PMID:Major approaches for generating and analyzing transgenic mice. An overview. 840 66

The wheat bZIP protein HBP-1a(17) is a putative transcription factor regulating histone gene expression. To delineate the functional domain(s) of this factor, we made a series of effector constructs expressing fusion proteins, in which various portions of HBP-1a(17) are fused to the DNA-binding domain of the yeast transcriptional activator GAL4, in plant cells. When the beta-glucuronidase (GUS) reporter gene, driven by the wheat histone H3 core promoter harboring the GAL4-binding sequence, was co-transfected with such effector genes into tobacco protoplasts, several portions of HBP-1a(17) influenced reporter gene expression. The N-terminal one-third of HBP-1a(17), termed the P region (residues 1-118) due to its Pro content, did not activate the reporter gene, in contrast to the corresponding Pro-rich region of Arabidopsis GBF1 (residues 1-110), which functions as an activation domain. When the P region was divided into two, however, both its N-terminal (1-56; termed NP) and C-terminal (58-118; termed PC) halves were able to enhance expression of the reporter gene. When the NP region was further divided into NP(5-30) and NP(30-56), both regions still retained activating ability. These results suggest that the P region of HBP-1a(17) is composed of several modules each having activating function, and modification and/or conformational changes of the P region might influence its function.
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PMID:Dissection of the wheat transcription factor HBP-1a(17) reveals a modular structure for the activation domain. 906 88

A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.
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PMID:Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase. 917 67

The role of salt (NaCl) in the development of high blood pressure has been a matter of debate, however, the Intersalt Study showed that sodium (Na) intake in various areas of the World is related to the slope of blood pressure with age. Accurate amounts of the total salt intake or that coming from a particular source are needed, both, for physicians who need to consider the salt intake of their patients and for public health workers who are in charge of the implementation of public health programs where salt is used as a carrier of other nutrients. An analysis of the literature suggests that exaggerated values for total salt intakes have often been obtained from indirect estimates; discretionary salt use, i.e. home-cooking salt has invariably been overestimated. A method is described for measuring the contribution of cooking salt to total salt intake since it is a confusing area where inappropriate methods have been used to assess its contribution. The method described is based on the use of small amounts of lithium carbonate fused with NaCl. Validation experiments were undertaken to determine the naturally occurring lithium (Li) in a number of foods including fresh, frozen and tinned vegetables, and the use of Li tagged salt for cooking vegetables and for direct use in cooked foods. We also assessed whether Li was taken up proportionally with Na into foods during cooking. In general vegetables contained variable but only small amounts of Li except aubergine and spinach, and Li was taken up proportionally with Na in a variety of vegetables. Results showed that 36, 35 and 21% of the salt added during cooking was recovered in carrots, runner beans and potatoes respectively, the rest being discarded in the cooking water. This suggest that about a third of salt added during the cooking of vegetables will be ingested by the household. Attempts to rely simply on the total use of household salt supplies will clearly exaggerate, markedly, the true intake of individuals.
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PMID:Defining cooking salt intakes for patient counselling and policy making. 923 39


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