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

19-Acetylenic-deoxycorticosterone (19-A-DOC) is believed to be a competitive irreversible inhibitor of the synthesis of 19-nor-deoxycorticosterone (19-nor-DOC), a potent mineralocorticoid implicated in some forms of human and animal hypertension. It has been shown to inactivate 11 beta/19-hydroxylase in hamster adrenal mitochondria. Dispersed bovine zona fasciculata cells were incubated for one hour with 1.5 x 10(-8) M ACTH and 0, 1, 10, or 100 microM 19-A-DOC and tritiated deoxycorticosterone (DOC) substrate. Steroids were separated using two sequential thin-layer chromatography systems and their tritium content was counted and corrected for recovery. The 19-A-DOC decreased synthesis of 19-hydroxydeoxycorticosterone, the precursor of 19-nor-DOC. The inhibitor also impaired 11-hydroxylation of DOC to form corticosterone. The data suggest that 19-A-DOC is an effective inhibitor of 11 beta/19-hydroxylase activity in dispersed bovine adrenal cells.
Steroids 1995 Mar
PMID:19-Acetylenic-deoxycorticosterone inhibits 19-hydroxylase and 11 beta-hydroxylase activities in dispersed bovine zona fasciculata cells. 779 29

Investigators in hypertension have extensively evaluated the mechanisms of hypertension as first described by Goldblatt in his classic clipped kidney models. Although renovascular hypertension appears to affect only 2-4% of the population referred for diagnostic studies of hypertension, our understanding of renovascular hypertension has broadened from the interaction of the renin-angiotensin system to the inclusion of the activation of the sympathetic nervous system and locally mediated prostaglandins. This increased understanding of renal mediated abnormalities has also led to the implication that abnormalities in renal function may be the main abnormality in primary hypertension. It has been demonstrated that early, mildly hypertensive patients may have an increase in total body volume. This elevated volume may lead to autoregulation which persistently elevates vascular resistance. The renal abnormality leading to an abnormal pressure-volume relationship may be related to a decrease in renal plasma flow mediated by an increase in arteriolar resistance. This increase in vascular tone has been ascribed to an increase in sympathetic nerve activity, an increase in renin and/or an increase in catechols and angiotensin II. It has also been suggested that ischemic nephrons in a microvascular model akin to the classic Goldblatt two kidney-one clip model may be the pathologic abnormality underlying primary hypertension. These concepts of renovascular hypertension and primary renal dysfunction are reviewed in this conference.
Steroids 1993 Dec
PMID:Mechanisms of renal hypertension and renal contribution to primary hypertension. 811 14

Several characteristics of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), make these homozygous strains particularly well suited for investigating the interactions of salt appetite, blood pressure control, and their neuroendocrine substrates. Appropriate genetic and developmental investigations of sources of variation in salt appetite, blood pressure, and their putative neuroendocrine substrates in these homozygous strains can provide valuable insights into fundamental mechanisms of disease, as well as factors controlling homeostatic behavioral and physiological processes. However, inappropriate use of these strains can produce misleading, although seductively plausible, conclusions regarding mechanisms. Selective inbreeding for hypertension has concentrated in SHR the "high pressure" allele for several genes that influence blood pressure, whereas breeding for normal blood pressure has left WKY with the "normal pressure" allele for all or most of these genes. In principle, inbred hypertensive strains could provide information about specific genetic alterations that mediate the hypertensive phenotype. The benefits of work with these strains are discussed, but several false assumptions and logical pitfalls are described that might cause misleading or erroneous interpretations of results from work with such strains. These problems illustrate the importance of the research strategy in elucidating the particular information that can be provided by these inbred animal models of hypertension. Two strategic approaches for studying hypertension and other genetically determined or influenced characteristics in inbred animal models such as SHR are discussed: cosegregation analysis for identifying or rejecting genetic linkage, and brain graft techniques for identifying brain specific genetic influences on cardiovascular or behavioral phenotypes. Examples of each approach are described.
Steroids 1993 Dec
PMID:Strategies for investigation of CNS mechanisms of phenotypic variation in blood pressure and salt appetite in genetic hypertensive rats. 811 15

Review of pertinent research demonstrates a link between sex steroids and vascular disease. Evidence for this association includes: beneficial effect of estrogens on the blood lipids (elevation of high-density lipoproteins and lowering of low-density lipoproteins), adverse effect of high-dose synthetic estrogens on coagulation, vasodilating action of progesterone, and adverse effect of androgens and androgen-derived progestagens on lipoproteins. Natural steroids appear to differ in their impact from synthetic compounds; endogenous hormones from exogenous and parenterally administered preparations. Furthermore, steroids have different effects at different concentrations, doses, and ratios. Their actions also vary according to age, sex, pregnant or nonpregnant state, body weight, smoking, and other risk factors. In this article, the following areas will be considered in relation to the impact of sex steroids on cardiovascular phenomena and hypertension: menstrual cycle and its disturbances; amenorrhea and hyperandrogenism; pregnancy with its hyperdynamic state and a tendency to gestational hypertension; oral-contraception-induced, dose-related thromboembolic phenomena; menopause and estrogen deficiency states with increased incidence of atherogenesis; estrogen replacement therapy with its decrease in cardiovascular morbidity; other hormonal therapies which induce hypoestrogenism with its consequences. The evidence is emerging that hormonal modifications may be useful in the prevention of cardiovascular morbidity.
Steroids 1993 Dec
PMID:The role of reproductive hormones in vascular disease and hypertension. 811 16

Mean mineralocorticoid receptor number in mononuclear leukocytes of patients with increased plasma aldosterone (Conn's syndrome, nephrovascular hypertension, preeclampsia) is lower than in controls and this reduction could be the consequence of a down-regulation of the receptor. A similar pattern is evident also in situations of excess of other mineralocorticoids (Cushing's syndrome, chronic licorice ingestion). In essential hypertension 20% of cases have reduced number of mineralocorticoid receptors in mononuclear leukocytes without increase of aldosterone and normal serum potassium. We postulate that in some cases with essential hypertension the reduction of mineralocorticoid receptors is an index of mineralocorticoid excess due to mineralocorticoids other than aldosterone.
Steroids 1993 Dec
PMID:Regulation of aldosterone receptors in hypertension. 811 17

The role of adrenal steroid hormones in hypertension has, until recently, focused on disorders of secretion. We describe a new form of mineralocorticoid hypertension which arises from impaired metabolism of physiological glucocorticoid. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is responsible for the inactivation of cortisol to cortisone. Congenital absence of this enzyme (the syndrome of apparent mineralocorticoid excess) results in cortisol acting as a potent mineralocorticoid. Furthermore, inhibition of this enzyme by glycyrrhizic and glycyrrhetinic acids also accounts for the mineralocorticoid excess states seen following licorice and carbenoxolone ingestion. Whilst impaired 11 beta-HSD activity has been shown in patients with "essential" hypertension, the significance of this finding remains unknown. These clinical studies, however, have uncovered a novel physiological mechanism, whereby the mineralocorticoid receptor (which in vitro has an equal affinity for cortisol and aldosterone) is protected from cortisol excess by the action of 11 beta-HSD. Thus 11 beta-HSD plays a crucial role in determining the in vivo specificity for this receptor.
Steroids 1993 Dec
PMID:Steroid hormones and hypertension: the cortisol-cortisone shuttle. 811 18

It has been postulated that insulin resistance and the concomitant compensatory hyperinsulinemia contribute to the pathogenesis of hypertension, possibly by stimulating the sympathetic nervous system, promoting renal sodium reabsorption, modulating cation transport, and/or stimulating vascular smooth muscle hypertrophy. The purpose of this article is to present a comprehensive up-to-date review of the literature and critically examine the insulin resistance-hyperinsulinemia-hypertension hypothesis.
Steroids 1993 Dec
PMID:Insulin and hypertension: are they related? 811 19

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the Type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the short-chain dehydrogenase family. Using site-directed mutagenesis, it was demonstrated that the amino terminus and two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11 beta-OHSD deficiency, did not reveal any mutations in the HSD11 gene. This disorder may involve an additional enzyme with 11 beta-OHSD activity or possibly another cortisol metabolizing enzyme.
Steroids 1994 Feb
PMID:Genetic analysis of 11 beta-hydroxysteroid dehydrogenase. 819 38

The syndrome of apparent mineralocorticoid excess (AME) is currently understood to reflect impaired peripheral metabolism of cortisol, which is then able to activate the non-selective mineralocorticoid (MC) receptor. The failure of glucocorticoid inactivation at the MC target tissue level in AME involves abnormal activity of 11 beta-hydroxysteroid dehydrogenase, with impaired conversion of cortisol to cortisone, and also of 5 beta-reductase. We have discovered a new form of AME (Type II) in four patients with the same clinical picture of hypertension, hypokalemia, and suppressed renin-angiotensin-aldosterone system, but in whom this conversion seems either to be normal (since cortisol to cortisone metabolite ratio is normal) or to be impaired in both directions, leaving the ratio unchanged. Both types are characterized by a profound decrease in cortisol turnover quotient and Ring A reduction constant. Short-term dexamethasone treatment is effective in correcting the MC-derived abnormalities, while in the long term the addition of other antihypertensive drugs may be required to control the severity of hypertension.
Steroids 1994 Feb
PMID:Apparent mineralocorticoid excess type II. 819 52

Elucidation of a role for 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in modulating ligand access to renal mineralocorticoid receptors, together with identification of expression of the enzyme in most mammalian tissues, has raised the possibility (i) that glucocorticoid metabolism might influence corticosteroid receptor activation in other sites which are relevant to blood pressure control (e.g., vascular smooth muscle), and (ii) that abnormal 11 beta-OHSD expression might play a pathogenic role in common forms of hypertension (e.g., essential hypertension and the syndrome of ectopic ACTH secretion). This article reviews data from human experiments which suggest that 11 beta-OHSD has tissue-specific actions which can increase or decrease sensitivity of both mineralocorticoid and glucocorticoid receptors to cortisol, and that assessment of cortisol sensitivity may prove equally important as assessment of cortisol secretion rates in hypertensive patients.
Steroids 1994 Feb
PMID:Organ-specific actions of 11 beta-hydroxysteroid dehydrogenase in humans: implications for the pathophysiology of hypertension. 819 53


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