摘要:

BackgroundResults of several studies have shown that subjects with white-coat hypertension (WCH) have more target-organ damage than do normotensive controls with similar ambulatory blood pressures.ObjectiveTo investigate whether this is due to a selection bias.SettingSeventeen hypertension clinics in northeast Italy.Main outcome measuresEchocardiographic data in relation to WCH status.Patients and methodsMild hypertensive subjects from the HARVEST (n = 565) who underwent two ambulatory blood pressure monitorings 3 months apart and M-mode echocardiography, and 95 normotensive control subjects.ResultsFrom first ambulatory monitoring, 90 hypertensive subjects were classified as having WCH (mean daytime blood pressure < 130/80 mmHg). Their 24 h blood pressure was similar to that of the normotensive subjects, but their left ventricular mass index was greater. From second ambulatory monitoring, only 38 of the 90 subjects still had WCH, whereas 24 h blood pressure in the other 52 had risen beyond the limit of WCH. Left ventricular mass index (89.2 ± 2.4 g/m2), wall thickness (18.1 ± 0.3 mm), and relative wall thickness (0.359 ± 0.006%) of the 38 subjects with WCH at both recordings were still greater than those of the normotensive subjects (82.4 ± 1.5 g/m2,P= 0.02; 17.2 ± 0.2 mm,P= 0.002; and 0.337 ± 0.004%,P= 0.025) and similar to those of the 52 subjects who no longer had WCH (88.5 ± 2.0 g/m2, 18.7 ± 0.2 mm, and 0.375 ± 0.005%, all NS).ConclusionsOwing to regression toward the mean, over 50% of the subjects with WCH could no longer be classified as such from repeated ambulatory monitoring, indicating that the current diagnosis of WCH is subject to selection bias. Cardiac remodeling was present also in the subjects confirmed to have WCH by repeated blood pressure recording, suggesting that the effect of WCH has an actual impact on target organs.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism might be involved in the development of several cardiovascular diseases, but its role in humans remains controversial.ObjectiveTo investigate the relation between the angiotensin converting enzyme gene polymorphism and extent of blood pressure elevation in arterial hypertension, taking into account the influence of cardiovascular risk factors.MethodsWe studied 171 patients (aged 49 ± 9 years, 61 women) with abnormal clinic and 24 h ambulatory blood pressures, after a 3-week wash-out.ResultsWe found no significant difference in clinic and ambulatory blood pressures among homozygotic D (DD), heterozygotic D (ID) and homozygotic I (II) angiotensin converting enzyme genotypes and between homozygotic D (DD) and pooled heterozygotic D (ID) plus homozygotic I (II) (non-DD) angiotensin converting enzyme genotypes. At least one additional cardiovascular risk factor (smoking, hypercholesterolaemia or diabetes) was present for 103 patients (33 DD and 70 non-DD). Non-DD subjects (n= 43) without additional cardiovascular risk factors exhibited lower values of 24 h, daytime systolic and pulse blood pressures than did members of all other groups (allP< 0.04). In the presence of risk factors, DD and non-DD subjects exhibited similar systolic and pulse ambulatory blood pressures, in that we found higher values in non-DD genotype subjects with risk factors than we did for non-DD subjects without additional risk factors. In multivariate analysis, the combination of non-DD genotype and absence of cardiovascular risk factors was associated with the lowest values of systolic and pulse blood pressures.ConclusionsAngiotensin converting enzyme insertion allele appears clustered with lower ambulatory systolic and pulse blood pressures in hypertensive patients when the potential interference of additional cardiovascular risk factors is eliminated. A high prevalence of cardiovascular risk factors in population studies might blunt a possible biological association of blood pressure with DD genotype by contributing to raising of blood pressures also in subjects with non-DD genotypes.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundSeveral cytokines and adhesion molecules released from endothelium play an important role in inflammation, immune responses, and probably atherogenesis.ObjectiveTo determine whether the transcription factor nuclear factor-κB mediated expression of these genes involved in the inflammatory response of endothelial cells to tumor necrosis factor-α, by using transcription factor decoy oligodeoxynucleotides.Design and methodsWe first transfected fluorescein isothiocyanate (FITC)-labeled double-stranded oligodeoxynucleotides into endothelial cells by a cationic liposome-mediated method of gene transfer. We then confirmed that the decoy oligodeoxynucleotides could block binding of nuclear factor-κB to its specific cis element effectively. In addition, we transfected the reporter gene chloramphenicol acetyltransferase driven by three repeated nuclear factor-κB binding sequences in the promoter and enhancer region.ResultsFITC-labeled oligodeoxynucleotides were detected in the nuclei of approximately 70% of the total cells. Tumor necrosis factor—stimulated expression of chloramphenicol acetyltransferase was partially inhibited by transfection of nuclear factor-κB decoy oligodeoxynucleotides, but not by transfection of scrambled oligodeoxynucleotides. Also nuclear factor-κB decoy oligodeoxynucleotides but not scrambled oligodeoxynucleotides inhibited tumor necrosis factorinduced expression of interleukin-6 and intracellular adhesion molecule-1 both at the messenger RNA and at protein level (assessed by reverse transcription—polymerase chain reaction and enzyme-linked immunosorbent assay).ConclusionOur results demonstrate that nuclear factor-κB decoy oligodeoxynucleotides transfected by cationic liposome method inhibited tumor necrosis factor —induced expression of interleukin-6 and intracellular adhesion molecule-1 in endothelial cells.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe oxidation of low-density lipoprotein (LDL) might play an important role in the development of atherosclerosis.ObjectiveTo establish whether greater than normal production of nitric oxide (NO)in vivoprotects LDL from oxidation.Patients and methodsWe studied nine subjects affected by Bartter's and Gitelman's syndrome (both characterized by greater than normal production of NO), and 10 subjects matched for age, sex and lipid levels as controls. LDL particles were isolated from plasma by density gradient ultracentrifugation. Susceptibility of LDL to oxidation was evaluated after incubation with copper sulfate solution, by measuring the formation of conjugated dienes, the thiobarbituric acid-reactive substances, and the volatile peroxidation products of n-3 (propanal) and n-6 (pentanal and hexanal) polyunsaturated fatty acids. Phospholipid fatty acid composition of LDL was determined by gas chromatography. LDL α-tocopherol concentrations were measured.ResultsPatients with Bartter's and Gitelman's syndrome had LDL particles smaller and/or denser than those of controls [Rf= 0.38 ± 0.03 versus 0.42 ± 0.02 (mean ± SD),P< 0.01], which hence were assumed to be more oxidizable. The phospholipid fatty acid composition of LDL and the α-tocopherol concentrations did not significantly differ between patients and controls. The duration of the lag phase, which is the time preceding formation of conjugated dienes, did not differ between groups, but the lag phase times were related to urinary excretion of nitrite/nitrate from patients (r= 0.66,P< 0.05). Moreover, patient LDL had produced less thiobarbituric acid-reactive substances after 5 h (P< 0.04), and less pentanal and hexanal after 5 and 6h (P< 0.04 andP< 0.02, respectively) than had that of controls.ConclusionsGreater than normal production of NOin vivois associated with lower than normal susceptibility of LDL to oxidationin vitro, suggesting that NO plays a protective role in the development of atherosclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that insulin resistance of the spontaneously hypertensive rat (SHR) and adrenocorticotropin-hypertensive rat is related to a difference in the proportion of the functionally different, alternatively spliced exon 11 isoforms of the insulin receptor.DesignWe determined the proportions of mRNA for the exon 11+ and exon 11− isoforms in various tissues of SHR and Wistar—Kyoto rats aged 3, 6, 9 and 12 weeks, which span the pre-hypertensive phase through to established hypertension, as well as in Sprague—Dawley rats with adrenocorticotropin-induced hypertension and Sprague—Dawley controls.MethodsDetection of mRNA involved a reverse-transcriptase polymerase chain reaction technique specific for each isoform and quantification was by slot and dot blot hybridization.ResultsMean proportions of exon 11+ mRNA in SHR, Wistar—Kyoto rats, adrenocorticotropin-hypertensive rats and Sprague—Dawley control rats at each age were 95% for liver, 82% for adipose tissue, 77% for kidney, 66% for adrenal, 53% for heart, 26% for cerebral cortex, 23% for hypothalamus, and 3% for skeletal muscle. There was also no difference in concentration of total insulin receptor mRNA.ConclusionsThe absence of any difference in proportions of insulin receptor mRNA isoforms argues against the hypothesis that an alteration of differential splicing plays a role in the models of hypertension studied.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundPrevious research with normotensive adults aged over 40 years (‘older’) found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2to high sodium intake was greater than normal.ObjectiveTo test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2.DesignForty-eight Caucasian men and women (age 28.5 ± 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume.ResultsSubjects with high end-tidal partial pressures of CO2had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2(by 0.8 ± 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 ± 0.8 mmHg) for the whole group. However, the changes in resting systolic (r= 0.32,P< 0.025) and diastolic (r= 0.36,P< 0.01) blood pressures and in 24 h systolic (r= 0.28,P< 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 ± 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2.ConclusionsThe results indicate that a high resting partial pressure of CO2augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare the effects of chronic administrations of the angiotensin II antagonist losartan and of the angiotensin I converting enzyme inhibitor enalapril on renal function in sodium-depleted rats with one-kidney, one clip hypertension, and to examine the contribution of endogenous kinins to the effect of enalapril.MethodsWe administered enalapril and losartan (10 and 30 mg/kg per day, respectively) for 6 days to hypertensive rats that had been subjected to dietary sodium-intake restriction for 6 days prior to treatment and continued to be subjected to this restriction during treatment. In an additional group, administration of enalapril was combined with infusion of the bradykinin B2-receptor antagonist Hoe 140 (300 μg/kg per day subcutaneously via an osmotic pump). Renal function of anesthetized rats was assessed by using a clearance technique.ResultsDespite there being similar falls in arterial pressure, glomerular filtration rate (867 ± 40 μl/min per g kidney weight in untreated rats) was decreased to a larger extent in enalapril-treated than it was in losartan-treated rats (284 ± 29 versus 438 ± 36 ml/min per g kidney weight,P< 0.01). Although infusion of Hoe 140 had no influence on the effect of enalapril on arterial pressure, the level of glomerular filtration achieved in rats of this group (545 ± 55 μl/min per g kidney weight) was similar to that found in losartan-treated rats. No effect of either treatment on renal plasma flow was detected; as a consequence, the excessive decrease in filtration fraction observed for rats in the enalapril-treated group was corrected by concomitant administration of Hoe 140. Interestingly, administration of enalapril resulted in a greater loss of sodium than did administration of losartan (723 ± 147 versus 308 ± 57 μmol during 6 days), and this effect was abolished by infusion of Hoe 140 (353 ± 42 μmol during 6 days).ConclusionAdministration of enalapril to sodium-depleted rats with one-kidney, one clip hypertension reduces their glomerular filtration rate to a greater extent than does administration of losartan despite these agents having similar effects on systemic blood pressure. Combined administration of enalapril and Hoe 140 has a less marked effect on glomerular filtration rate than does that of enalapril alone. This suggests that kinins play a role in the regulation of efferent arteriolar tone in this rat model.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo investigate pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans.Design and methodsSeventeen human hearts were studied. Group 1 consisted of control hearts (four hearts, weighing 280 ± 40 g each), from subjects who had had no evidence of heart disease and for whom the diagnoses of death were noncardiac. Groups 2 (five hearts, weighing 440 ± 50 g each), 3 (five hearts, weighing 560 ± 50 g each), and 4 (three hearts, weighing 680 ± 60 g each) consisted of hearts from subjects who had had a history of systemic hypertension. All hearts had no valvular deformities and no evidence of ischemic disease at the postmortem examination. A cell-maceration method was employed to evaluate the myocardial connective matrix after removal of the nonfibrous elements of myocardial tissue, leaving behind a noncollapsed matrix, thus allowing a better three-dimensional view. Myocardial tissue was also processed for conventional light microscopic and morphometric studies.ResultsThe minor transverse diameter of myocytes from hearts in groups 1–4 hearts were 13.7 ± 7.8, 23.7 ± 3.4, 26.6 ± 3.7, and 32.8 ± 5.8 μm, respectively. The volume fraction of fibrosis of the controls was 6.5%, whereas the volume fractions in hypertensive hearts increased progressively according to heart weight: 15.4, 22.9, and 31.1% for hearts in groups 2, 3, and 4, respectively. The most striking feature was the diffuse marked increase in amount of pericellular collagen weave fibers (endomysial matrix), parallel to the increase of heart weight. The hypertrophied myocytes were encased in a dense weave of collagen fibrils continuous with those of adjacent myocytes. The muscle fibers in hypertrophied hearts were markedly larger than normal, although this was extremely variable from an area to another. Besides, a diffuse increase in the number of thick collagen fibers constituting broad bands and sheets of collagen surrounding disorganized muscle bundles (perimysial matrix) was observed. Scattered dense scar-like foci, apparently replacing areas of myocyte loss, could be seen, mainly on the periphery of muscle bundles. This latter finding was more commonly observed among hypertrophied hearts from group 3 and, mainly, among hypertrophied hearts of group 4. Importantly, a progressive disarray of the connective tissue skeleton of the myocardium could be seen in parallel to the progressive increase of cardiac hypertrophy.ConclusionsThe progressive accumulation of interstitial collagen fibers in left ventricular hypertrophy, in parallel to an increase in heart weight, can be expected to contribute to a spectrum of ventricular dysfunction involving either the diastolic or systolic phase of the cardiac cycle, or both, that is associated with the greater than normal arrhythmogenic risk for a hypertensive heart. Moreover, the methodology used is useful for studying the spatial organization of the collagen fibrils of the myocardium under normal and pathologic conditions.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo study the relationship between serum cholesterol level and left ventricular mass for a population of untreated hypertensive patients.DesignA cross-sectional study.PatientsWe studied 273 untreated hypertensive patients without associated diseases consecutively referred for evaluation of blood pressure. All patients underwent M-mode echocardiographic assessment of left ventricular mass, office blood pressure measurement and 24 h ambulatory blood pressure monitoring. Fasting plasma glucose and total cholesterol levels were measured on the same day.ResultsWe found a weak but significant correlation (r= 0.20–0.26,P< 0.01) between serum cholesterol level and left ventricular wall thickness or left ventricular mass irrespective of the mode of indexation used (height, height2.7and body surface area). In multivariate analysis this relation remained significant after introduction of sex, age, weight, height, blood pressure and blood glucose level. When data for men and women were analysed separately the relationship between left ventricular mass and cholesterol remained significant for men only.ConclusionThere is a significant and independent positive relationship between serum cholesterol level and left ventricular mass that could contribute to the prognostic value of left ventricular hypertrophy.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare 2.5 mg bendrofluazide daily (the standard antihypertensive dose), 1.25 mg bendrofluazide daily and 2.5 mg bendrofluazide on alternate days, in terms of reduction of blood pressure, patient compliance and adverse effect profile.DesignA single-blind parallel group trial of patients who were randomly assigned to 16 weeks' treatment with bendrofluazide at doses of 2.5 mg daily, 1.25 mg daily and 2.5 mg every other day after a 4-week placebo run-in period.SettingGeneral practices in the greater Belfast and Lisburn area in Northern Ireland.PatientsNinety-three patients with newly diagnosed or previously diagnosed hypertension, who had a mean diastolic blood pressure of 90–110 mmHg after receiving placebo for 4 weeks.Main outcome measuresReduction in blood pressure, patient compliance and changes in biochemical variables.ResultsSitting systolic and diastolic blood pressures in members of all three groups were significantly lowered with respect to baseline (P< 0.01) with no differences among groups. Overall mean compliance was 97%. No clear relation between dose and biochemical changes was apparent.ConclusionsBendrofluazide at doses of 1.25 mg daily or 2.5 mg every other day reduces blood pressure as effectively as does the conventional 2.5 mg daily regimen.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID