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

This study was made to determine whether zinc deficiency is one of the factors involved in growth retardation of infants of high-risk pregnancies. The high risk factors were hypertension of pregnancy, diabetes mellitus, congenital heart disease, chronic nephritis, rheumatic heart disease and hyperthyroidism. 102 neonatal infants were divided into 3 groups: breast fed group, 37 cases; test group, 32 cases formula-fed with supplementary zinc 1.14-2.28 mg/kg/d; and control group, 33 cases formula-fed and supplemented with Vitamin B complex as placebo. The groups were divided by double-blind and randomized method. There were no differences in the 3 groups in sex ratio, growth status and serum zinc concentration at the beginning of the study. Anthropometric data were obtained at 0, 3 and 6 months.
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PMID:Growth promoting effect of zinc supplementation in infants of high-risk pregnancies. 129 Dec 3

Cells were isolated from the outer medulla of the rabbit kidney, primarily from the thick ascending limb of Henle's loop (mTALH). These mTALH cells are heavily invested with a cytochrome P450-linked monooxygenase that represents the third pathway by which arachidonic acid is metabolized. After cell separation, approximately 80% of the cells proved to be mTALH in origin, based on electron microscopic criteria and immunofluorescent localization of Tamm-Horsfall protein, a specific marker for mTALH cells. The specific activity of alkaline phosphatase, a marker for proximal tubular cells, decreased threefold after separation of mTALH cells from outer medullary cells, associated with a fourfold increase in the capacity of the separated mTALH cells to metabolize arachidonic acid. Incubation of mTALH cells with 14C-arachidonic acid resulted in formation of oxygenated metabolites, identified as two peaks (P1 and P2), which accounted for 30 to 40% of the recovered radioactivity. Formation of prostaglandin E2 and F2 alpha accounted for only 3 to 5%. The chromatographic retention times of P1 and P2 were different from products of lipoxygenases. An inhibitor of cytochrome P450-dependent enzymes, SKF-525A (50 microM), reduced product formation by mTALH cells by more than 70%, while induction of cytochrome P450 increased product formation. Formation of P1 and P2 by cell-free homogenates of mTALH was totally dependent on the presence of nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), which suggests a NADPH-dependent cytochrome P450-linked monooxygenase pathway. Vasopressin and calcitonin (10(-10) M to 10(-7) M) stimulated release of arachidonic acid metabolites from mTALH cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Renal arachidonic acid metabolism. The third pathway. 298 23

Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95% endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent Km value of 11.11 microM and an apparent Vmax of 3-OH benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis.
Hypertension
PMID:Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta. 407 22

The expression of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11HSD) activity has been investigated in the epidermis and appendages of the human skin. Aldosterone binds to MR and regulates sodium transport in tight epithelia. Mineralocorticoid selectivity is achieved through coexpression of MR and 11HSD, which prevents permanent MR occupancy by glucocorticoids. Some forms of hypertension may involve abnormalities of MR and/or 11HSD. However, their direct assessment in humans remains difficult in the kidney or colon. This led us to explore this system in human skin easily accessible to biopsy. In situ hybridization with specific MR complementary ribonucleic acid probes and immunohistochemistry using three different anti-MR antibodies showed that MR was expressed at both the messenger ribonucleic acid and protein levels in the keratinocytes of the epidermis, in the sweat and sebaceous glands, and in the hair follicles. A significant 11HSD activity was found in isolated sweat gland ducts (5 fmol/3-mm length.10-min incubation with 10 nmol/L corticosterone as substrate) and was very low in the epidermis. In both structures, reductase activity was 10 times lower than that of dehydrogenase. Studies on the cofactor specificity of the enzyme showed a nicotinamide-adenine-dinucleotide preference in sweat glands, contrasting with a nicotinamide-adenine-dinucleotide phosphate dependence in epidermis. Human skin appears as a new target for aldosterone because it coexpresses MR and 11HSD. Our findings present the possibility to explore the functionality of the MR system in human tissue and its implications in various physiopathological situations.
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PMID:Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase. 796 26

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the conversion of cortisol to cortisone and plays an important role in the mammalian kidney in regulating cortisol access to the mineralocorticoid receptor. 11 beta HSD-deficient states, such as the syndrome of apparent mineralocorticoid excess (AME), and licorice ingestion result in hypertension in which cortisol acts as a mineralocorticoid. A gene and complementary DNA sequence encoding type I human 11 beta HSD have been described, but this gene is normal in patients with AME. Separate 11 beta HSD isoforms have been described in rat and rabbit kidney, but 11 beta HSD has not been characterized in human kidney. Kinetic analysis of 11 beta HSD activity in human fetal kidney microsomes revealed only a high affinity isoform (apparent Km, 60 nmol/L for cortisol, 13 nmol/L for corticosterone), the activity of which was exclusively nicotinamide adenine dinucleotide (NAD) dependent. No 11-oxo-reductase activity was seen in either renal homogenates or microsomes. 11 beta-Dehydrogenase activity was inhibited by glycyrrhetinic acid (the active ingredient in licorice) in a competitive fashion, with a Ki of 8.7 nmol/L. This 11 beta HSD isoform was clearly distinct from the type I h11 beta HSD enzyme, in that COS-1 cells transfected with type I h11 beta HSD complementary DNA expressed a low affinity (apparent Km, 2.13 mumol/L) isoform, the activity of which was NAD phosphate dependent. 11-Oxo-reductase activity was present in intact transfected cells (apparent Km for cortisone, 0.36 mumol/L), but not in cell lysates. In contrast to the cloned, low affinity, type I h11 beta HSD enzyme, human kidney contains a high affinity NAD-dependent 11 beta HSD isoform. It seems probable that this isoform is responsible for protecting the renal mineralocorticoid receptor from glucocorticoid excess, and a defect in its activity may explain AME.
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PMID:Human kidney 11 beta-hydroxysteroid dehydrogenase is a high affinity nicotinamide adenine dinucleotide-dependent enzyme and differs from the cloned type I isoform. 804 66

No differences were found in the rate of metabolism of vitamins B1, B2, B6 and niacin either in healthy persons or in patients with duodenal ulcer, hypertension of the 2nd degree and with ischemic heart disease as shown by excretion of riboflavin, 4-pyridoxylic acid, 1-methyl nicotinamide and thiamin with urine which correlated with concentration of these vitamins and their coenzyme forms in blood plasma and erythrocytes. Dependence of these vitamins excretion with urine on their concentration in blood and the vitamins content in food appear to demonstrate similar consumption of vitamins B in the persons studied; at the same time, evaluation of the vitamins consumption in the patients with these forms of pathology should be performed using the criteria suitable for healthy persons. Dissimilar rates of metabolism of these vitamins described in literature might be related to differences in nutrition as well as to the use of nonspecific techniques for estimation of the vitamins. Besides, initial consumption of vitamin B2 was not sometimes considered, but deficiency in riboflavin caused considerable impairments of vitamin B6 and niacin metabolism.
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PMID:[B group vitamin metabolism in duodenal ulcer disease, hypertension, and ischemic heart disease]. 816 Apr 30

With retrograde tracing using fluorogold injection into the superior cervical ganglion and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, the present comparative study revealed that the retrogradely labelled neurons in n. intermediolateralis pars funicularis (ILf) and n. intermediolateralis pars principalis (ILp) of the autonomic region in the upper thoracic cord exhibited a much stronger reactivity for NADPH-diaphorase in Wistar-Kyoto (WKY) rats than those in spontaneously hypertensive rats (SHR). It was found that in ILf in WKY rats, 77.62% of the fluorogold-labelled neurons were NADPH-d positive, while in SHR, only 56.43% of the labelled neurons were NADPH-d positive. The frequency distribution of NADPH-d positive retrogradely labelled neurons was significantly reduced in ILf of the spinal cord of SHR (U-test: P < 0.01). In ILp in WKY rats, 65.25% of fluorogold-labelled neurons were NADPH-d positive in WKY rats, while in SHR, only 56.28% of the labelled neurons were NADPH-d positive. Although the difference (P > 0.05) in the frequency of NADPH-d positive neurons in ILp between the two strains of rats was not significant, the reductions in SHR seemed considerable. Examination of the preganglionic sympathetic trunk and the superior cervical ganglion between SHR and WKY rats revealed that virtually all the NADPH-d positive fibers were derived from the sympathetic preganglionic neurons. In SHR, the NADPH-d positive fibers were not as intensely stained as those of WKY rats. This preliminary results suggest that nitric oxide, as an inhibitory neurotransmitter, may be implicated in the onset of hypertension.
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PMID:A comparative study of NADPH-diaphorase in the sympathetic preganglionic neurons of the upper thoracic cord between spontaneously hypertensive rats and Wistar-Kyoto rats. 859 47

CONVERSION OF CORTISOL TO CORTISONE: 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) is a microsomal enzyme complex which, in humans, catalyses the interconversion between biologically active cortisol and inactive cortisone. This prereceptor signalling mechanism is essential for maintaining the aldosterone selectivity of the intrinsically non-specific mineralocorticoid receptor and for modulating glucocorticoid access to the glucocorticoid receptor. Apparent mineralocorticoid excess (AME) is a syndrome of severe low-renin mineralocorticoid hypertension associated with marked hypokalaemia which arises from a congenital deficiency of 11 beta-HSD. In AME patients, therefore, it is cortisol and not aldosterone which behaves as a potent mineralocorticoid. ISOFORMS OF 11 BETA-HSD: Two isoforms of human 11 beta-HSD have now been characterized and cloned. The type 1 isoform (11 beta-HSD1) is a low-affinity reduced nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenase-oxoreductase which is expressed in predominantly glucocorticoid target tissues and the encoding sequence of which is normal in patients with AME. In contrast, the type 2 isoform (11 beta-HSD2) is a high-affinity NADP-dependent unidirectional dehydrogenase which is expressed in placenta and mineralocorticoid target tissues such as renal collecting ducts and distal colonic epithelia. Exon- and intron-specific polymerase chain reaction amplification of the 11 beta-HSD2 gene from genomic DNA from members of a consanguinous kindred with AME consistently revealed a single missense mutation (C1228T) in two affected sibs and twin stillbirths. This mutation in codon 374 of exon 5 of the 11 beta-HSD2 gene creates an inframe premature stop (TGA) and, as such, results in a truncated 11 beta-HSD2 protein lacking the carboxyl-terminal proline-rich 32 amino acids. In keeping with an autosomal recessive mode of inheritance, both parents were phenotypically and biochemically normal but were heterozygous for this mutation. Unique to this kindred were expression analyses of the native mutant 11 beta-HSD2 enzyme in the stillbirth-affected placenta, which was almost completely devoid of NADP-dependent 11 beta-dehydrogenase activity. Immunohistochemical and Western blot analyses revealed the absence of 11 beta-HSD2 protein using antisera raised against synthetic peptide sequences corresponding either to the carboxyl terminus or other domains of the enzyme. MISSENSE MUTATION: In this kindred with AME, congenital deficiency of 11 beta-HSD activity is due to a single missense mutation in exon 5 of the 11 beta-HSD2 gene. Simultaneous studies by two other groups have similarly revealed no gross deletions or rearrangements of the 11 beta-HSD2 gene, but have described a number of single point mutations and oligonucleotide deletions in exons 3, 4 and 5, and adjacent to a splice site in intron 3. Recombinant expression analysis of site-directed mutant 11 beta-HSD2 complementary DNA constructs suggests a correlation between the predicted severity of these mutations and the biochemical and clinical phenotype. AME AS A CAUSE OF HYPERTENSION: The mutations in the 11 beta-HSD2 gene, together with those currently being sought by us for other kindreds with AME, establishes AME as a monogenic cause of human hypertension and will provide insight into the structure-function relationships of this important enzyme.
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PMID:Human hypertension caused by mutations in the 11 beta-hydroxysteroid dehydrogenase gene: a molecular analysis of apparent mineralocorticoid excess. 912 Jun 78

Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources. In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially. Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase. This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions. Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane-bound, reduced nicotinamide-adenine dinucleotide (NADH)-dependent oxidase. The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin. Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis.
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PMID:Endothelial function and oxidant stress. 942 47

Recent evidence suggests a role for reactive oxygen species in the control of vascular smooth muscle proliferation both in vitro and in vivo. Oxidative stress increases cell proliferation, mediates hormone-induced hypertrophy, and-under some circumstances-induces apoptosis. Smooth muscle cells contain a reduced nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide phosphate oxidase that is responsible for the majority of the superoxide produced by the vessel wall. This enzyme has been characterized biochemically, but only limited information is available regarding its molecular structure. High levels of oxidative stress are apparently involved in the pathogenesis of vascular diseases such as hypertension and atherosclerosis, along with abnormal vascular growth after balloon injury. Thus the pathways responsible for oxidative stress, as well as the antioxidant defenses in the vessel wall, may provide novel therapeutic targets.
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PMID:Redox control of vascular smooth muscle proliferation. 966 66


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