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

The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was used to study the hormonal control of angiotensinogen synthesis and release in the rat. Dexamethasone administration in vivo resulted in increase in the in vitro rate of release of angiotensinogen by liver slices into the incubation media. This increase was inhibited by actinomycin D, an inhibitor of protein synthesis and vincristine which blocks secretion. Similarly, ethinyl estradiol treatment resulted in a 50% increase in angiotensinogen production. Hyperthyroid state was achieved by injecting rats with L-thyroxine daily for seven days. Hepatic production rate of angiotensinogen rose 21/2-fold above control and was accompanied by increases in plasma angiotensinogen concentration and plasma renin activity. In contrast, plasma angiotensinogen concentration and plasma renin activity were reduced in thyroidectomized rats. The rate of angiotensinogen production by liver slices of these rats decreased by five-fold below that of intact animals. These changes were largely corrected when thyroidectomized rats were treated with replacement doses of L-thyroxine. We conclude that hepatic angiotensinogen biosynthesis is under hormonal control. Glucocorticoid, estrogen and thyroid hormones all stimulate angiotensinogen production. These results may in part explain the pathogenesis of hypertension associated with certain disease states.
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PMID:Hormonal control of angiotensinogen production. 704 Aug 93

The role of angiotensinogen in blood pressure control was assessed in normotensive rats by observing the changes resulting from inhibition by specific rat angiotensinogen antiserum. The antiserum decreased blood pressure in rats on normal sodium as well as sodium-free diets (respectively delta BP = -30 +/- 6 mm Hg and -42 +/- 8 mm Hg). In binephrectomized sodium-replete rats, administration of antiserum did not reduce blood pressure, whereas in sodium-depleted animals it slightly decreased blood pressure by 11 +/- 3 mm Hg. These results suggest that angiotensinogen participates in the regulation of blood pressure in normotensive rats, even in the sodium-replete state.
Hypertension
PMID:Role of angiotensinogen in blood pressure homeostasis. 706 78

It can be estimated that women using hormonal contraceptives develop hypertension at a rate of 1% to 2%. This occurs within 6 to 12 weeks after beginning the contraceptive. As for the extent of the elevation, it varies from slight elevations of systolic and/or diastolic pressure up to serious, even malignant hypertension including nephrosclerosis. Although the latter is rare, it underlines the importance of keeping careful check on women taking these pills. After cessation of the pill the blood pressure drops in a greater or lesser proportion of the women within 3 to 6 months. Some authors say 8-12 months. No antihypertensive therapy is required for this. The blood pressure elevation correlates regularly with parallel changes in the renin-angiotensin-aldosterone-system. This is caused mainly by the estrogen component of the hormonal contraceptive. It is manifested by overproduction of angiotensinogen in the liver with subsequent elevation of angiotensin II. Finally there is a sharp vasoconstriction and increase in aldosterone production which cause systemic blood pressure elevation. It can be postulated that sodium retention, and genetic predisposition to react to elevation of the whole-body sodium content by an increase in blood pressure, are determining for the pathogenesis of this condition. The appropriate conclusions should be drawn as concerns the prescription of hormonal ocntraceptives in medical practice.
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PMID:[Hormonal contraception and hypertension]. 708 May 44

An apparent high molecular weight angiotensinogen (H-Aogen) can be separated from the usually predominant low molecular weight angiotensinogen (L-Aogen) by gel filtration of plasma. H-Aogen has been quantitated in plasma from normotensive menstruating women, estrogen treated women, normotensive pregnant women, women with pregnancy-induced hypertension (PIH), and women whose preexisting hypertension was exacerbated during pregnancy. When expressed as a percent of the total angiotensinogen, the H-Aogen levels were: menstruating women 4%, estrogen-treated women 10%, normotensive pregnant women 16%, women with PIH 25%, and pregnant women with exacerbated hypertension 28%. A significant difference (p less than 0.01) was found between H-Aogen concentration in normotensive pregnant women and women with PIH (1.10 +/- 0.12 and 1.73 +/- 0.16 micrograms angiotensin I/ml plasma respectively). In some hypertensive pregnant women, H-Aogen is the predominant form of angiotensinogen. Thus, H-Aogen should be recognized as a component of the renin-angiotensin system.
Hypertension
PMID:High molecular weight angiotensinogen levels in hypertensive pregnant women. 710 39

One approach to establish the existence and functionality of a brain angiotensin system is to demonstrate selective alterations in that system following perturbation of peripheral cardiovascular functions. The present study utilized this approach to quantify regional angiotensinogen levels in the rat brain following bilateral nephrectomy, a perturbation that severely disrupts salt and water homeostasis. Angiotensinogen, the precursor of any centrally-derived angiotensin, was analyzed since it should provide a marker for a putative angiotensin peptidergic system. Net brain angiotensinogen was determined by correcting total tissue concentrations of angiotensinogen with accurate values of contaminating plasma angiotensinogen. The latter was determined by quantifying regional plasma space utilizing tritiated inulin as a marker of cerebral vascular space. It was found that there were no detectable alterations in regional net brain angiotensinogen in the first 24 hours following nephrectomy despite over a twofold increase in plasma angiotensinogen and the absence of significant plasma renin. By 32 hours postnephrectomy, certain areas of the rat hypothalamus and midbrain exhibited significant elevations in net angiotensinogen content. These areas coincided with regions traversed by neural pathways shown to mediate angiotensin-induced drinking or blood pressure elevations. The results lend further support to the concept of an independent brain angiotensin system.
Hypertension
PMID:Regional changes in rat brain angiotensinogen following bilateral nephrectomy. 714 8

The presence of a renin-angiotensin system in the central nervous system (CNS) has been demonstrated by several investigators, but little is known regarding the origin of its components. In this study we have compared the immunological and physical-chemical nature of angiotensinogen in plasma and cerebrospinal fluid (CSF) of human subjects and explored whether differences are present in CSF angiotensinogen concentrations of normal and hypertensive subjects. No significant differences in the nature of plasma and CSF angiotensinogen was observed with respect to molecular weight (65-70,000) electrophoretic mobility (RFalb = 0.67 plus or minus 0.003) or angiotensin I (AI) generated (pI = 6.6). Following isoelectric focusing, the plasma angiotensinogen was shown to consist of a single component with an isoionic point of 4.40 plus or minus 0.04. CSF angiotensinogen, on the other hand, resolved into three components (pI = 4.76 plus or minus 0.02; 5.16 plus or minus 0.04; 5.76 plus or minus 0.04). Although no correlations were observed between angiotensinogen levels in the CSF or plasma with blood pressure (BP), a statistically significant difference in angiotensinogen concentration of both plasma and CSF was observed between normotensive and hypertensive subjects. The differences in the chemical and immunological nature of human plasma and CSF angiotensinogens suggest that the angiotensinogen of CSF is not of peripheral origin.
Hypertension
PMID:Studies on angiotensinogen of plasma and cerebrospinal fluid in normal and hypertensive human subjects. 739 27

Oral contraceptive (OC) use is discussed as a factor in various diseases and disorders of internal medicine. Studies show a significant increase in the risk of developing thromboembolism, pulmonary embolism, cerebrovascular incidents, and coronary infarction among OC users. These problems are caused by changes in blood coagulation, hemodynamics, fibrinolysis, and the damaging of vascular walls, all of which are attributable to OC use. OC use leads to a minor hypertension in 1% of users during the first year of use and in 2.5% by the fifth year. This is initially caused by increased angiotensinogen production in the liver; later, sodium retention caused by the gestagen OC component, mineralocorticoid activity and vascular damage play a part in causing this hypertension. Glucose tolerance is reduced by OCs; lipid metabolism is affected in many ways: e.g. elevation of plasma triglyceride levels. OC users run an increased risk of developing hepatic tumors. Jaundice, Budd Chiari syndrome, gall stones, and pancreatitis have all been observed among OC users. Contraindications to OC use are listed.
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PMID:[Internal medicine problems regarding contraception. Part I]. 744 16

A higher frequency of a variant of the angiotensinogen gene characterized by a transition in exon 2 causing a replacement of methionine by threonine (M235T) has recently been found in hypertensive individuals, but not all authors were able to confirm this observation. We examined (i) 219 patients with primary hypertension, (ii) 92 normotensive controls (spouses), and (iii) a sample of the general population (blood donors, n = 139). Analysis of genomic DNA was performed by PCR amplification and alleles were separated on agarose gels. In the general population and in normotensive spouses the respective frequencies of the T and M alleles were: general population: M = 0.6, T = 0.4; normotensive spouses: M = 0.59, T = 0.41. A significantly higher frequency of the 235T allele was found in hypertensive individuals with a family history of hypertension and an onset of hypertension before 50 years of age (spouses: 0.41 versus HT with age of onset < or = 50 years and family history of HT: 0.56; P = 0.01 by chi 2). In conclusion, the present study confirms the observation of a higher frequency of the 235T allele of the angiotensinogen gene in hypertension and identifies individuals with family history and early onset of hypertension as individuals at risk.
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PMID:Association of M235T variant of the angiotensinogen gene with familial hypertension of early onset. 747 15

Angiotensin-converting enzyme inhibitors have proven to be uniquely effective in inducing regression, or preventing the occurrence, of ventricular hypertrophy associated with systemic hypertension. This has pointed, for many years, to a possible direct involvement of the renin-angiotensin system in the pathogenesis of cardiac hypertrophy. Over the last 10 years further supporting evidence has been forthcoming about direct trophic effects of angiotensin II in several experimental systems. Additionally, we now have rather conclusive evidence for the existence of a local, intracardiac renin-angiotensin system, which is capable of synthesis of all components of the system, and of cleaving, via the classic pathway, angiotensin peptides from the precursor, angiotensinogen. Moreover, a number of studies have demonstrated the capacity of regulatory response and modulation of activity of the local system in response to a variety of pharmacologic perturbations as well as differential expression of specific components under pathologic conditions, including compensatory hypertrophy and remodeling after myocardial infarction, pressure overload hypertrophy, and volume overload hypertrophy. Continued research into the role of the cardiac renin-angiotensin system in the pathogenesis of cardiac hypertrophy and failure will provide us with the tools to devise more specific, targeted strategies for therapeutic intervention or prevention.
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PMID:The cardiac renin-angiotensin-aldosterone system and hypertensive cardiac hypertrophy. 749 12

Genetic approaches provide a new insight into the understanding of biological mechanisms underlying blood pressure regulation and hypertension. Some progress has been made in elucidating the molecular mechanisms of rare forms of hypertension. Common forms of hypertension are likely to be due to combinations of DNA variants of several genes involved in blood pressure regulation. Only little progress has been made in the identification of the underlying genetic factors, due to the complex nature of this disease. Experimental crosses of hypertensive rats offer an ideal setting for the genetic dissection of mammalian physiology. With the opportunity to study inbred rat strains the problem of genetic heterogeneity becomes irrelevant. Cosegregation studies investigating candidate genes for hypertension have been carried out for a number of genes. Moreover, systematic mapping of quantitative trait loci involved in blood pressure regulation has recently become possible in genetically hypertensive rat models. In contrast, genetic studies involving hypertensive individuals are currently limited to the investigation of candidate genes in association and sib-pair analysis. So far, the angiotensinogen gene is the only locus that has been implicated in the pathogenesis of human hypertension in association as well as sib-pair analysis. Considering the complexities of genetic hypertension, animal models will play an important role in the genetic dissection of this disease. A critical prerequisite for the study of human hypertension is the availability of large patient and family cohorts.
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PMID:Genetics in arterial hypertension--clinical and experimental aspects. 749 77


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