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1. |
The role of the 11β‐hydroxysteroid dehydrogenase type 2 in human hypertension |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 241-248
Paolo Ferrari,
Emanuela Lovati,
Felix Frey,
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摘要:
The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme inactivates 11β-hydroxy steroids in sodium-transporting epithelia such as the kidney, thus protecting the non-selective mineralocorticoid receptor (MR) from occupation by cortisol in humans. Inhibition by xenobiotics such as liquorice or mutations in the HSD11B2 gene, as occur in the rare monogenic hypertensive syndrome of apparent mineralocorticoid excess (AME), result in a compromised 11βHSD2 enzyme activity, which in turn leads to overstimulation of the MR by cortisol, sodium retention, hypokalaemia, low plasma renin and aldosterone concentrations, and hypertension. Whereas the first patients described with AME had a severe form of hypertension and metabolic derangements, with an increased urinary ratio of cortisol (THF+5αTHF) to cortisone (THE) metabolites, more subtle effects of mild 11βHSD2 deficiency on blood pressure have recently been observed. Hypertension with no other characteristic signs of AME was found in the heterozygous father of a child with AME, and we described a girl with a homozygous gene mutation resulting in only a slightly reduced 11βHSD2 activity causing ‘essential’ hypertension. Thus, depending on the degree of loss of enzyme activity, 11βHSD2 mutations can cause a spectrum of phenotypes ranging from severe, life-threatening hypertension in infancy to a milder form of the disease in adults. Patients with essential hypertension usually do not have overt signs of mineralocorticoid excess, but nevertheless show a positive correlation between blood pressure and serum sodium levels, or a negative correlation with potassium concentrations, suggesting a mineralocorticoid influence. Recent studies revealed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites in some patients with essential hypertension.These abnormalities may be genetically determined. A genetic association of a HSD11B2 flanking microsatellite and hypertension in black patients with end-stage renal disease has been reported. A recent analysis of a CA-repeat allele polymorphism in unselected patients with essential hypertension did not find a correlation between this marker and blood pressure. Since steroid hormones with mineralocorticoid action modulate renal sodium retention, one might hypothesize that genetic impairment of 11βHSD2 activity would be more prevalent in salt-sensitive as compared with salt-resistant subjects. Accordingly, we found a significant association between the polymorphic CA-microsatellite marker and salt-sensitivity. Moreover, the mean ratio of urinary cortisol to cortisone metabolites, as a measure for 11βHSD2 activity, was markedly elevated in salt-sensitive subjects. These findings suggest that variants of the HSD11B2 gene may contribute to the enhanced blood pressure response to salt in some humans.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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2. |
Hypertension and breast cancer risk in a 19‐year follow‐up study (the DOM cohort) |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 249-254
Petra Peeters,
Paulus van Noord,
Arno Hoes,
Jacques Fracheboud,
Charles Gimbrère,
Diederick Grobbee,
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摘要:
BackgroundTo investigate whether hypertension and the use of anti-hypertensive drugs are associated with breast cancer risk.MethodsThis was a prospective study of 11 011 women living in Utrecht, the Netherlands, aged 50–65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985 at which blood pressure was measured and information on drug use and breast cancer risk factors was ascertained. Since 1974 (median follow-up time 19 years), information on breast cancer occurrence and death has been registered. Hypertension was defined as a systolic blood pressure >160 mmHg or a diastolic blood pressure >95 mmHg or current use of drugs for the indication hypertension. Cox's regression analysis was used to investigate the association between hypertension (treated or untreated) and subsequent breast cancer risk. Analyses were adjusted for age, body mass index, height, parity, familial breast cancer, smoking and oral contraceptive use.ResultsA total of 523 women were diagnosed with breast cancer. Hypertensive women experienced a statistically significant increased breast cancer risk of 23% (age-adjusted hazard ratio (HRa) = 1.23; 95% confidence interval (CI) 1.01–1.49). After adjustment for all confounders, the increase was 14% (HR = 1.14; 95% CI 0.93 ± 1.40). The decline in risk was mainly attributable to the effect of BMI. The risk was similar in treated (HR = 1.22; 95% CI 0.91–1.63) and untreated hypertensive women (HR = 1.13; 95% CI 0.91–1.40).ConclusionThese results do not support an association between hypertension and breast cancer, and if there is a link, it is likely to be positive and relatively small in size (+14%). This relation, if present, is not attributable to anti-hypertensive drugs, since the relation is also present in non-drug users.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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3. |
Blood pressure levels and obesity trends in hypertensive and normotensive Finnish population from 1982 to 1997 |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 255-262
Mika Kastarinen,
Aulikki Nissinen,
Erkki Vartiainen,
Pekka Jousilahti,
Heikki Korhonen,
Pekka Puska,
Jaakko Tuomilehto,
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摘要:
ObjectiveTo assess the trends in blood pressure (BP) and in body mass index (BMI) in the hypertensive and normotensive population in Finland during 1982–1997.DesignFour independent cross-sectional standardized population surveys were conducted in 1982, 1987, 1992 and 1997.SettingThe provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in southwestern Finland.ParticipantsMen and women aged 25–64 years were selected randomly from the national population register. The participants were classified into four groups according to their BP level and treatment status: normotensive, unaware hypertensive, aware but untreated hypertensive and treated hypertensive. The total number of participants was 24 083.Main outcome measuresThe means of systolic BP (SBP), diastolic BP (DBP) and BMI, as well as the distribution of BMI among the four study groups were measured.ResultsMean SBP decreased significantly in all groups. The fall in DBP was significant only in drug-treated hypertensive men and women (P<0.001). Mean BMI increased significantly in all groups except in aware hypertensive women receiving no antihypertensive drug treatment. The proportion of obese subjects (BMI >30 kg/ m2) increased most in aware hypertensive men and in drug-treated hypertensive women.ConclusionsThe prevalence of obesity has increased significantly in normotensive and particularly in hypertensive Finns during the past 15 years. There is an urgent need for more effective measures for weight reduction in obese hypertensive patients in primary healthcare, and for the prevention and control of obesity in the whole population.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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4. |
Evaluation of heterodimeric guanylyl cyclase genes as candidates for human hypertension |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 263-266
Robert Danziger,
Chris Pappas,
Craig Barnitz,
Tena Varvil,
Steven Hunt,
Mark Leppert,
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摘要:
ObjectiveBoth physiologic and pharmacological data have implicated the nitric oxide (NO) signaling cascade in the regulation of blood pressure in humans and its impairment in the pathogenesis of hypertension. In biological systems, the principal receptor for NO is NO-stimulated guanylyl cyclase. NO-stimulated guanylyl cyclases are obligate heterodimers (α/β). The genes for guanylyl cyclase subunits α1, β1, and β2are likely candidates for causing hypertension in the Dahl rat as their expression is altered and their gene loci are closely linked to known quantitative trait loci for blood pressure in Dahl rat crosses. The objective of the current study was to test whether markers near guanylyl cyclase subunit genes were linked to hypertension in Caucasians.DesignTo test for linkage of genetic markers in or near the guanylyl cyclase genes to hypertension in Caucasians, a sample of 124 Utah hypertensive sib pairs was genotyped.ResultsFour highly polymorphic markers in or near the human guanylyl cyclase subunits homologous to the rat α1(human chromosome 8), rat β1(human chromosome 4), and rat β2(human chromosme 13) genes showed no evidence of excess allele sharing in the set of hypertensive sibships.ConclusionWe conclude that the heterodimeric guanylyl cyclase subunit loci do not appear to be linked to hypertension in Caucasians.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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5. |
Evaluation of three polymorphisms in the promoter region of the angiotensin II type I receptor gene |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 267-272
Xun Zhang,
Jeanette Erdmann,
Vera Regitz-Zagrosek,
Susanne Kürzinger,
Hans-Werner Hense,
Heribert Schunkert,
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摘要:
BackgroundAngiotensin II induces vasoconstriction and growth via stimulation of the AT1receptor. A genetic variant (+1166A/C) in the 3′ untranslated region of this gene had been found to be associated with arterial hypertension, aortic stiffness and coronary artery disease.ObjectiveIn order to evaluate further the potential implications of the genetic variability of the AT1gene we explored three newly characterized single nucleotide polymorphisms (SNPs) in its promoter in a Caucasian population-based sample (n= 623). One of these (−2228G/A) is in complete linkage disequilibrium with six additional SNPs in the region such that, indirectly, potential functional implications of these sites were assessed as well. For comparison, we genotyped the previously described +1166A/C variant.ResultsThe allele frequencies of the −2228G/A, −1424C/ G and −521C/T SNPs were 0.82/0.18, 0.963/0.037 and 0.64/0.36, respectively. Statistical analysis by one-factor ANOVA revealed no significant relationship of any allele, genotype or haplotype with age, sex, body mass index, heart rate, systolic or diastolic blood pressure, hypertension, the intake of antihypertensive medication or left ventricular mass. Likewise, renin, angiotensinogen, angiotensin-converting enzyme, aldosterone or atrial natriuretic peptide levels were not found to be associated with any of these SNPs. Surprisingly, the −2228 A allele was found to be overrepresented in subjects with diabetes mellitus (n= 25,P= 0.006). However, this result could not be confirmed when additional individuals with diabetes mellitus (n= 45) were analysed. A weak linkage disequilibrium was observed between the −2228 A allele and the +1166 C allele (χ213.1;P= 0.010).ConclusionFrom the present data it is unlikely that any one of the nine newly characterized SNPs in the promoter region of AT1gene is associated with arterial hypertension.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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6. |
Receptor‐ and non‐receptor‐mediated clearance of bigendothelin and endothelin‐1differential effects of acute and chronic ETAreceptor blockade |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 273-279
Mick Burkhardt,
Matthias Barton,
Sidney Shaw,
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摘要:
AimsThe aims of this study were to define and characterize the different mechanisms and sites of clearance of plasma endothelin-1 (ET-1) and big endothelin-1 (BigET-1) and evaluate possible effects of ETAversus combined ETAand ETBreceptor blockade or endothelin converting enzyme (ECE) inhibition.MethodsTime courses and sites of clearance were evaluated in Wistar-Kyoto rats after bolus injection of radiolabelled peptides into the carotid artery before or after treatment with LU135252 (ETA) and bosentan (ETAand ETB) as receptor antagonists or the ECE inhibitor phosphoramidon.ResultsThe study shows that differential clearance of125I-ET-1 and125I-BigET-1 is mediated by distinct tissue-specific, receptor- and non-receptor-mediated mechanisms. Low levels of plasma ET-1 are rapidly cleared, mainly in the pulmonary circulation, through a low-capacity saturable ETBreceptor-linked mechanism. In contrast, BigET-1 clearance is markedly slower, confined largely to liver and kidneys, is essentially non-receptor-mediated and is independent of converting enzyme activity. Acute inhibition of both ETAand ETBreceptors with bosentan dramatically prolonged125I-ET-1 plasma half-life and shifted tissue uptake from lung to liver and kidneys. Pulmonary clearance of125I-ET-1 was decreased by chronic but not acute treatment with the specific ETAreceptor antagonist LU135252. In contrast,125I-Big-ET-1 clearance and tissue uptake were essentially unchanged by all treatments.ConclusionsPlasma levels and clearance studies on ET-1 and BigET-1 may provide differential information regarding pathological changes in their separate uptake mechanisms. Such data could have diagnostic or prognostic value in pulmonary, hepatic and renal pathophysiology or future therapeutic monitoring of treatment efficacy following administration of selective receptor antagonists.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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7. |
Assessment of arterial and cardiopulmonary baroreflex gains from simultaneous recordings of spontaneous cardiovascular and respiratory variability |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 281-286
Daniela Lucini,
Alberto Porta,
Olivia Milani,
Giuseppe Baselli,
Massimo Pagani,
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摘要:
ObjectivesIn usual models of cardiovascular regulation, arterial pressure drives RR interval through a simple baroreflex, and the influence of respiration is dismissed. We examined the applicability of a trivariate autoregressive model to obtain separate values of the gain of the arterial and non-arterial, i.e. cardiopulmonary, components of the lumped baroreflex, employing spontaneous RR interval, systolic arterial pressure and respiration variability.DesignWe studied 30 normal subjects (age 37 ± 1 years), both at rest and during standing, a condition known to enhance sympathetic activity while reducing venous return. Electrocardiogram was obtained by telemetry, arterial pressure by Finapres and respiration with a piezoelectric respiratory belt. Data were acquired with a PC and processed with an ad hoc Windows program.MethodsWe employed an additive and a linear multivariate approach to approximate overall gain of the arterial pressure-heart beat period baroreflex (αlumped) and of its arterial (αart) and non-arterial, i.e. cardiopulmonary (αcp), components, from continuous beat-by-beat series of RR interval, systolic arterial pressure variability and respiration, without using any non-physiological intervention.ResultsThe overall baroreflex gain at rest (αlumped= 23.7 ± 3.4 ms/mmHg) was subdivided into arterial (αart= 5.2 ± 1.0 ms/mmHg) and cardiopulmonary (αcp= 18.5 ± 3.2ms/mmHg) components. During active orthostatism, αlumpedwas diminished to 10.0 ± 2.2 ms/ mmHg. In addition, standing selectively reduced αcpto 4.8 ± 1.3 ms/mmHg, while αartwas not significantly changed.ConclusionsA trivariate autoregressive model, that considers explicitly the influence of respiration, can subdivide overall, lumped, arterial pressure-heart period baroreflex gain, into two separate components, αartand αcp. Only the latter is reduced by active orthostatism.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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8. |
Inhibitory effect of insulin on bradykinin‐induced venodilation |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 287-292
Masahiko Kimura,
Hiroshi Watanabe,
Reiko Takahashi,
Kazuhiro Kosuge,
Kazuo Umemura,
Hideharu Hayashi,
Kyoichi Ohashi,
Ryuzo Ohno,
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摘要:
BackgroundExcessive insulin is one of the risk factors of hypertension and arteriosclerosis despite its vasodilative properties shown in recent studies. Although many vasoactive substances contribute and interact with each other in the development of hypertension, the interactions between insulin and other vasoactive substances have yet to be elucidated.ObjectiveTo assess the effect of insulin on the action of bradykinin.MethodsThe vasodilating effect of bradykinin was evaluated, with or without coadministration of insulin, in human dorsal hand veins of healthy volunteers. In cultured porcine aortic endothelial cells, the bradykinin-induced increase of intracellular calcium was also investigated before and after insulin administration.ResultsInsulin significantly attenuated bradykinin-induced increase in intracellular calcium and venodilation in cultured endothelial cells and human dorsal hand veins, respectively.ConclusionsThese findings suggest that insulin attenuates the bradykinin-induced calcium elevation in endothelial cells and may decrease the production of vasodilative substances from endothelial cells, resulting in the reduction of vasodilation. This effect may contribute to the development of hypertension in patients with hyperinsulinaemia.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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9. |
Change in common carotid artery diameter, distensibility and compliance in subjects with a recent history of impaired glucose tolerancea 3‐year follow‐up study |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 293-300
Robert van Dijk,
Giel Nijpels,
Jos Twisk,
Mieke Steyn,
Jacqueline Dekker,
Robert Heine,
Ab Donker,
Coen Stehouwer,
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摘要:
ObjectiveTo assess the development of common carotid artery properties (diameter, distensibility and compliance) in a cohort of 140 subjects (mean age 65.8 years, SD 7.5 years) originally diagnosed as impaired glucose tolerant in a population-based study, and to explore determinants of changes observed.DesignAn observational, longitudinal study over a 3-year-period.MethodsVessel wall movement detector system based on ultrasonography, linear generalized estimating equations.ResultsCarotid artery diameter rose from 6.87–7.02 mm (+ 2.2%,P< 0.001). Distensibility decreased from 11.8 to 10.9 × 10−3kPa−1(−8.3%,P= 0.009). Compliance decreased from 0.44–0.43 mm2kPa−1(P= 0.17). Changes in blood pressure level were negatively associated with changes in distensibility and compliance. Baseline fasting glucose levels were positively associated with changes in diameter, while fasting insulin levels were negatively associated with changes in distensibility and compliance in men, but not in women.ConclusionsIn subjects with a recent history of impaired glucose tolerance, we observed an increase in carotid artery diameter and a decrease in distensibility. Change in blood pressure level and baseline fasting glucose and HbA1c levels were positively related to the increase in diameter. In men, but not in women, baseline fasting insulin levels were associated with an acceleration of these changes.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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10. |
Ambulatory blood pressure and neuroendocrine control after diet‐assisted gastric restrictive surgery |
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Journal of Hypertension,
Volume 18,
Issue 3,
2000,
Page 301-306
Philippe van de Borne,
Isabelle Watrin,
Marie Bouquegneau,
Axelles Gilles,
Jean-Jaques Houben,
Françoise Fery,
Jean Degaute,
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摘要:
BackgroundLong-term weight control after conventional diet is disappointing but may be improved when diet is assisted by gastric restrictive surgery (GRS).ObjectiveTo determine the effects of GRS on ambulatory blood pressure (ABP) and neuroendocrine BP control in 28 morbidly obese subjects.MethodsA BP and heart rate were recorded every 10 min for 25 h before and 4 months after GRS. Effects of marked reductions in body weight on the renin-angiotensin-aldosterone system, on plasma insulin and on sympathetic activity were also determined.ResultsBody mass index decreased from 43 ± 1 to 34 ± 1 kg/m2and systolic (S) BP decreased by 7 ± 2 mmHg during daytime (P= 0.01) and by 8 ± 3 mmHg during the night (P= 0.02). Pulse pressure, a marker of reduced arterial compliance, decreased by 5 ± 1 mmHg throughout the 24 h period (P<0.001). Diastolic BP remained unchanged. Heart rate decreased more during the night (−13 ± 2 bpm,P<0.0001) than during daytime (−5 ± 2 bpm,P= 0.03). Reductions in SBP were largest in subjects with highest initial BP values (r= 20.63,P<0.001) but were unrelated to weight loss. GRS decreased fasting glycaemia, plasma insulin, plasma C peptide and 24 h urine sodium (n= 20) and noradrenaline (n= 19) excretion (P<0.01).ConclusionsDiet-assisted GRS favourably affects neuroendocrine BP control in obese patients. Reductions in sodium intake, insulin levels and sympathetic tone combined with possible improvements in arterial compliance induce persistent 24 h reductions in SBP and pulse BP. Reductions in BP are largest in subjects with highest initial BP values and are unrelated to the amount of weight loss, thereby emphasizing the importance of even moderate reductions in weight on BP control.
ISSN:0263-6352
出版商:OVID
年代:2000
数据来源: OVID
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