摘要:

DesignTo clarify the role of oxidative damage in essential hypertension, levels of lipid peroxidation products (malondialdehyde and lipofuscin) and activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were examined during a short period of physical exercise.Patients and methodsWe studied 11 male patients with mild to moderate essential hypertension in World Health Organization classes I or II and 10 healthy male controls. Physical exercise was performed on a bicycle ergometer at graded intensities of 1.0, 1.5 and 2.0 W/kg body weight. Plasma concentrations of lipofuscin, malondialdehyde, epinephrine, norepinephrine, insulin, free fatty acids and glucose were determined. Superoxide dismutase activity was analysed in erythrocytes and glutathione peroxidase activity in whole blood.ResultsConcentrations of lipofuscin and malondialdehyde were significantly elevated in hypertensive patients. Superoxide dismutase activity was not different between groups, while glutathione peroxidase activity was significantly decreased in hypertensive subjects. During exercise, the concentration of malondialdehyde and antioxidant enzyme activities increased significantly in both groups. No differences were found in absolute increases between the normotensive and hypertensive subjects. The levels of glucose, insulin and free fatty acids were similar in both groups. Basal concentrations of catecholamines and also the exercise-induced increases were lower in hypertensive patients.ConclusionsOur results indicate increased oxidative damage in patients with essential hypertension, which might be caused by a decrease in the activity of glutathione peroxidase. The ability of superoxide dismutase and glutathione peroxidase to respond to increased production of reactive oxygen species during a short period of physical exercise was not impaired in hypertensive subjects.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundWe have demonstrated that accumulated macrophages in human coronary arteries strongly express angiotensin converting enzyme in accordance with the development of atheromatous plaques. However, there are few reports on the regulation of the renin-angiotensin system in macrophages and in monocytes as their source.ObjectiveTo examine whether the renin-angiotensin system is upregulated during the differentiation of monocytes to macrophages, and whether it is further regulated by angiotensin II and cytokines.Materials and methodsWe used a human leukemia cell line, THP-1, for monocytes. Differentiated THP-1, induced by adding phorbol 12-myristate 13-acetate for 24 h, were used as macrophages. Expression of messenger RNA of the renin-angiotensin system components was measured by quantitative reverse-transcriptase polymerase chain reaction. Angiotensin converting enzyme activity and subtype-specific angiotensin-binding sites of cultured cells, and angiotensin II production in the culture medium were measured.ResultsMacrophages expressed all components of the renin-angiotensin system except chymase. Cellular angiotensin converting enzyme activity and angiotensin II in the medium were increased 3.2and 4.5-fold during differentiation, respectively. Expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors was increased 6.2and 6.4-fold during differentiation, and was sustained for 7 days. Incubation with angiotensin II for 24 h caused downregulation of both AT1and AT2receptor messenger RNA, but the expression levels were still more than threefold higher compared with monocytes. The density of binding sites of AT1and AT2receptors in macrophages was 0.26 ± 0.02 and 0.15 ± 0.01 fmol/106 cells, respectively.ConclusionThe renin-angiotensin system is markedly activated during monocyte/macrophage differentiation, and may participate in the development of atherosclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundStudies using cell cultures and animal models have indicated an important role for angiotensin II in atherosclerosis. In humans, at least two major enzymes are involved in the conversion of angiotensin I to angiotensin II: so-called angiotensin-converting enzyme (ACE) and chymase. Enhanced activation of chymase in atherosclerotic tissue homogenates has been reported in animal models, but its contribution to the generation of angiotensin II has not been studied.ObjectiveTo clarify the localization of chymase and its pathophysiologic role in the formation of angiotensin II, using human coronary arteries.Design and methodsTwenty-four coronary artery segments obtained from 14 autopsied patients were characterized histologically into the following categories: normal coronary arteries with diffuse intimal thickening, hypercellular lesions, atheromatous plaques and fibrosclerotic plaques. We compared the cellular localization of chymase, ACE and angiotensin II expression using immunocytochemical techniques.ResultsChymase was expressed only in the cytosole of mast cells in all segments. On the basis of the histologic study, the number of chymase-positive cells in the intima of atheromatous plaques was significantly higher than that in normal coronary arteries with diffuse intimal thickening. The expression of angiotensin II in the intima was enhanced in hypercellular lesions and atheromatous plaques. Localization of angiotensin II in the intima was associated with that of ACE. Immunodouble staining did not show colocalization of angiotensin II and chymase.ConclusionsThese results suggest an important role for the production of angiotensin II by ACE in the progression of atherosclerosis in human coronary arteries. Enhanced expression of chymase appears not to be involved in angiotensin II production in the intima.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe renin-angiotensin system plays a central role in blood pressure regulation, both by affecting renal function and by modulating vascular tone and structure. Recent studies in rodents demonstrated the existence of several components of this system in adipose tissue. The activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in obesity-associated hypertension. Few data are available on the presence of renin-angiotensin system components in human adipose tissue.Materials and methodsIn order to explore the expression of renin-angiotensin system genes in human adipose tissue and adipocytes, total RNA was isolated from whole adipose tissue (subcutaneous and omental) or cultured adipocytes (mammary) and subjected to reversetranscriptase polymerase chain reaction with primers specific for human angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors.ResultsAngiotensinogen, angiotensin converting enzyme and type 1 angiotensin receptor genes were widely expressed, both in human adipose tissue and in cultured human adipocytes. Furthermore, we found expression of the chymase and renin-binding protein genes in these samples.ConclusionsOur findings suggest the presence of a local renin-angiotensin system in human adipose tissue, with adipocytes being an important part of this system, and prompt speculation that this local renin-angiotensin system may be involved in obesity-related disorders, including hypertension and the metabolic syndrome.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe variability of the blood pressure response to blockade of the angiotensin II type 1 receptor is influenced by renin status and pharmacokinetics and pharmacokinetic-Spharmacodynamic interactions.ObjectiveTo compare the pharmacokinetic-pharmacodynamic interactions of two doses of an ester prodrug of a noncompetitive angiotensin II type 1 receptor antagonist, candesartan cilexetil, at 8 and 16 mg, with those of the reference angiotenisn II type 1 receptor blocker, losartan, at the standard dose (50 mg), in a human model that controls renin status.Design and methodsIn a double-blind placebo-controlled crossover study, we compared the effects on renin and mean blood pressure over 24 h of single oral doses of candesartan cilexetil at 8 and 16 mg and losartan at 50 mg in 16 sodium-depleted normotensive subjects.ResultsThe area under the curve (0–24 h) for plasma active renin did not differ significantly between 8 mg candesartan cilexetil and 50 mg losartan, but was significantly higher for 16 than for 8 mg candesartan cilexetil or for 50 mg losartan. The area under the curve (0–24 h) for the fall in mean blood pressure with 16 mg candesartan cilexetil (−2197 ± 96 mmHg/h) was significantly greater than that for placebo (−112 ± 81 mmHg/h;P< 0.05) but the difference was not statistically significant compared with either 8 mg candesartan cilexetil (−158 ± 95 mmHg/h) or 50 mg losartan (−144 ± 66 mmHg/h). The area under the curve (0–24 h) for the fall in mean blood pressure did not significantly differ between 8 mg candesartan cilexetil, 50 mg losartan and placebo. The area under the curve (0–24 h) for plasma active renin was significantly correlated to that for plasma levels of the active metabolite of losartan, EXP 3174 (r= 0.65,n= 16,P< 0.01). No such correlation was detected for each single dose of candesartan cilexetil but a dose-response relationship was present when both doses were combined.ConclusionsThe pharmacodynamic effects of a single oral dose of 16 mg candesartan cilexetil are greater than those of 50 mg losartan and 8 mg candesartan cilexetil. The variability in the pharmacokinetic-pharmacodynamic interaction is less pronounced for candesartan than for EXP 3174, which could result in reduced variability of the blood pressure effects in patients.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundLeft ventricular mass is associated with body size, obesity and blood pressure. Echocardiography is routinely used to estimate this parameter, which is usually indexed to body surface area to allow comparisons to be made between individuals and groups of different body size. However, in obese subjects, using left ventricular mass indexed to body surface area may inappropriately normalize left ventricular mass.ObjectivesThe aim of this study was to investigate the relationships between left ventricular mass and body composition and to determine the best determinants of left ventricular mass.Subjects and methodsEchocardiography and dual-energy X-ray absorptiometry were performed in 106 subjects under primary care. Half were hypertensive subjects and the others were normotensive age-and sex-matched control subjects. Univariate correlations were studied between left ventricular mass and height, height1.5, height2.7, weight, body surface area, body mass index, waist: hip ratio, fat-free mass, bone mineral content and fat mass. Stepwise multiple linear regression was performed to determine the best determinants of left ventricular mass.ResultsFat-free mass was correlated with left ventricular mass (r= 0.53,P= 0.0001) and was the only independent predictor of left ventricular mass (R2= 0.30,P= 0.0001) by multivariate analysis. Fat mass did not correlate with left ventricular mass (r= 20.005,P= 0.96). Other measures of body size, including body surface area, waist: hip ratio, bone mineral content, weight, height, height1.5, height2.7and body mass index all were correlated with, but were not independent determinants of, left ventricular mass.ConclusionsLeft ventricular mass is independently determined by fat-free mass but by no other measures of body size or composition. Specifically, left ventricular mass was neither correlated with nor determined by fat mass. None of the other measures of body size determined left ventricular mass. It may be more appropriate to index left ventricular mass to fat-free mass rather than to measures of body size which include fat mass.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAtrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide belong to a family of hormones that have natriuretic and vasodepressor activity and may play a pathophysiologic role in hypertension, heart failure and renal failure. Whereas immunoreactive human forms of these three natriuretic peptides are found in renal tubules, it is not clear whether they are derived from the systemic circulation or from local production.ObjectiveTo examine the gene expression of natriuretic peptides in cultured human glomerular cells.Materials and methodsWe sought to determine the presence of messenger RNA encoding for these natriuretic peptides using polymerase chain reaction following reverse transcription. The polymerase chain reaction products were confirmed by direct sequencing. Atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide in cell-culture supernatants were measured by radioimmunoassays (with detection limits of 2.1, 2.1 and 0.21 pmol/l, respectively).ResultsAtrial natriuretic peptide messenger RNA was not found in mesangial or glomerular epithelial cells (despite stimulation with tumor necrosis factor-α) except when the cells were cultured with a high concentration of fetal bovine serum (> 10%). Similarly, this peptide was not detected in supernatant unless the cells were cultured with fetal bovine serum at concentrations of > 10%. Brain natriuretic peptide messenger RNA was readily detected in cultured mesangial and glomerular epithelial cells with a lower concentration in the former. Brain natriuretic peptide was not found in the supernatant of resting mesangial cells but became detectable when incubated with tumor necrosis factor-α or fetal bovine serum. C-type natriuretic peptide messenger RNA was detected in mesangial and glomerular epithelial cells with a higher concentration in the latter. C-type natriuretic peptide was detected in the supernatant of resting glomerular epithelial cells and levels rose when incubated with increasing concentrations of tumor necrosis factor-α or fetal bovine serum. However, C-type natriuretic peptide was not detected in the supernatant of resting mesangial cells and remained undetectable following incubation with tumor necrosis factor-α or fetal bovine serum.ConclusionOur results suggest differences in the synthesis of natriuretic peptides between glomerular mesangial and epithelial cells.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID