ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

For many years now, silent ischaemia has been recognized as a distinct clinical entity, and its relevance in different patient groups has been established. However, a number of basic questions have not been answered. In explaining the pathophysiology of silent ischaemia, factors affecting both the demand and the supply side are now being recognized. With the exception of certain well-defined groups, it is not clear why some patients are mostly symptomatic, while other patients are predominantly asymptomatic. There appear to be many factors influencing the ischaemic pain threshold. Studies investigating the prevalence of silent ischaemia show a remarkably high prevalence of silent ischaemia in different patient groups. Patients with hypertension but without coronary artery disease form a specific and vulnerable high-risk population that is particularly prone to silent ischaemia. Since changes at the macrovascular level are not responsible, various factors negatively influencing either cardiac supply or demand have been investigated. A reduced coronary reserve is central in explaining the increased prevalence of silent ischaemia in hypertensives. Left ventricular hypertrophy renders meaningful detection of ST segment changes difficult, but a possible solution dealing with this problem is offered by applying more stringent criteria in terms of minimal ST depression in the definition of ischaemia. The treatment of silent ischaemia is largely the same as for angina pectoris, but whether therapy should be directed at elimination of all ischaemic episodes or only of symptomatic episodes depends on further prospective work addressing this question.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In addition to their role as sex hormones, it has been known for many years that oestrogens have protective effects on the vasculature. These have been implicated in the reduced incidence of cardiovascular disorders in premenopausal women and in post-menopausal women receiving oestrogen replacement therapy. This protection has been found to be due, in part at least, to direct effects of oestrogens on blood vessels. This review will summarize the available literature regarding oestrogenic effects on vascular contractility. Two major influences of oestrogens will be discussed; first the genomic effects induced by chronic administration of steroid hormones, and second, the rapid effects on vascular smooth muscle by non-genomic, and as yet not fully identified, mechanisms. In so doing, the diversity of oestrogenic actions on vascular contractility will be highlighted and the protective role of these agents against adverse cardiovascular events discussed.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveA family history of hypertension, obesity, diabetes mellitus, hypercholesterolaemia and hypertriglyceridaemia have all been associated with the risk for hypertension. We evaluated whether the clustering of these risk factors increases the risk for hypertension or whether the accumulation of risk factors is associated with the blood pressure level in non-hypertensive subjects.Methods and subjectsWe assessed the clinical data and family history of hypertension (in parents and siblings) for 9914 individuals (6163 men and 3751 women, 18–89 years old) who were screened in Okinawa, Japan, in 1997.ResultsIn 9914 subjects (2465 hypertensive and 7449 non-hypertensive subjects), all the five factors were positively associated with hypertension. The odds ratios (95% confidence interval) for the number of risk factors were 1.88 (1.62–2.18) for one risk factor, 3.06 (2.62–3.57) for two, 5.25 (4.37–6.30) for three, 8.71 (6.48–11.72) for four and 24.48 (8.49–70.56) for five, after adjusting for age, sex, alcohol consumption, cigarette smoking and physical exercise habits. In non-hypertensive subjects, multivariate regression analyses showed that the number of risks was positively correlated with blood pressure; the regression coefficient was 1.96 (P< 0.0001) for systolic blood pressure, and 1.47 (P< 0.0001) for diastolic blood pressure after adjusting for age and sex.ConclusionsClustering of risk factors was significantly associated with hypertension. The number of risk factors positively correlated with the blood pressure levels in nonhypertensive subjects. The accumulation of risk factors may play an important role in the pathogenesis of hypertension, and thus the aggregation of risk factors may need to be addressed in primary prevention efforts related to hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivePost-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen.Design and methodsSixteen healthy and normotensive post-menopausal women (age 55 ± 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17β-oestradiol plus cyclic norethisterone acetate (NETA) or placebo in two 12-week periods separated by a 3-month washout. Clinic blood pressure was measured sitting by the same observer with a mercury manometer at four visits in each period. Twenty-four hour ambulatory blood pressure was measured at baseline and in the ninth weeks of treatment in both periods.ResultsClinic systolic and diastolic BP were reduced after 10 days of oestradiol (−5.1 and −3.2 mmHg respectively,P≤ 0.05). After 9 weeks of cyclic HRT, prior to progestogen addition, clinic BP returned to baseline. During addition of NETA, diastolic blood pressure was again reduced (−3.6 mmHg,P= 0.037). Mean 24 h ambulatory systolic and diastolic blood pressures were significantly lower than clinic measurements (−15.7 and −5.9 mmHg,P≤ 0.001) but were unaffected by HRT.ConclusionsClinic blood pressure is reduced during a cyclic HRT regimen but the reduction varies with the HRT regimen, which might explain the diversity in previous BP findings during HRT. Norethisterone acetate might possess additive blood pressure-lowering effects in post-menopausal women.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThis study was designed to test the hypothesis that non-genetic factors such as age, gonads and maternal environment modulate the expression of the salt-susceptibility genes and affect the blood pressure response to salt-loading (salt-sensitivity and salt-resistance) in the Sabra rat model of hypertension.MethodsThe blood pressure response to salt-loading was studied in Sabra hypertension prone (SBH/y) and Sabra hypertension resistant (SBN/y) rats of both sexes: (1) at 1, 3, 6, 9 and 12 months of age, (2) in adult rats after orchiectomy or oophorectomy, and (3) in animals that had been raised and nourished from birth to weaning by a foster mother from the contrasting strain. In each of the study protocols, systolic blood pressure was measured at baseline by the tail cuff method, animals were salt-loaded with deoxycorticosterone acetate, and blood pressure was measured again after 4 weeks.ResultsBasal blood pressure at all the ages studied and in both sexes was on average 10–15 mmHg higher in SBH/y than in SBN/y. Salt-loading in SBN/y of both sexes aged 1–12 months did not induce any significant increment in blood pressure. Salt-loading in SBH/y, in contrast, caused a highly significant rise in systolic blood pressure, of 40 mmHg or more at all the ages studied. There was no age difference or sex dependence in the magnitude of the blood pressure response to salt. Oophorectomy or orchiectomy did not affect the levels of basal blood pressure nor prevent the hypertensive response to salt-loading in SBH/y or the lack of a hypertensive response in SBN/y rats. Gonadectomy did not affect blood pressure in salt-loaded hypertensive SBH/ y nor in salt-loaded normotensive SBN/y. The basal blood pressure and the blood pressure responses of SBH/y and SBN/y of both sexes raised by foster mothers of the contrasting strains from birth to weaning were not different from those observed when raised by their natural mothers.ConclusionsThis study indicates that salt-sensitivity in SBH/y and salt-resistance in SBN/y are not age-dependent phenomena; that the magnitude of the BP response to salt-loading is not sex-dependent; and that neither gonadectomy nor the maternal environment affect the blood pressure response to salt-loading in the adult animal of either strain. These non-genetic factors thus do not modulate expression of the salt-susceptibility genes in the Sabra genetic model of salt-sensitive hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThe evidence linking activation of the renin— angiotensin system with accelerated cerebro-vascular atherosclerosis remains controversial. We therefore prospectively investigated the relationships of plasma renin activity and aldosterone levels with carotid artery lesions (CAL) in essential hypertension.MethodsWe evaluated the prevalence and severity of CAL and the intimal—medial thickness (IMT) with a high-resolution echo-Doppler technique in 107 cerebrovascularly asymptomatic consecutive primary hypertensives (55 male, 52 female) and in 70 (42 male, 28 female) normotensive controls. We also measured supine plasma renin activity (PRA) and aldosterone before and 45 min after captopril administration, while daily urinary excretion of sodium was measured.ResultsBoth the prevalence (59.4 versus 26.2%) and severity of sex- and age-adjusted and unadjusted CAL and IMT were significantly higher in hypertensives than in controls. Regression analysis showed different predictors of IMT (age and captopril-stimulated-PRA,R2= 0.27,P< 0.0001), score of CAL (mean blood pressure,R2= 0.15,F= 12.73,P< 0.0001) and maximal stenosis (pulse pressure and known duration of hypertensionR2= 0.29,F= 14.58,P< 0.0001). Sex- and age-adjusted IMT did not differ between quartiles of renin-sodium profile. However, patients in the quartile with the highest PRA had the lowest score of CAL and an inverse relationship between age-adjusted PRA and IMT and CAL was found.ConclusionsThese results, besides confirming an association of both IMT and CAL with primary hypertension and ageing, demonstrate that CAL and IMT have different correlates. However, they do not support the contention that a high renin-sodium profile carries an excess risk of CAL in primary hypertensives with no clinical evidence of cerebro-vascular disease.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the molecular mechanisms of the anti-apoptotic action of hepatocyte growth factor (HGF), a novel angiogenic growth factor that may have a pivotal role in the regulation of endothelial cells, on human aortic endothelial cells.MethodsAn index of cell number and death was determined using a water-soluble tetrazolium salt dye assay, DNA fragmentation enzyme-linked immunosorbent assay, and non-confocal fluorescence microscopy of nuclear staining with Hoechst 33258 and propidium iodide. Extracellular-signal-regulated protein kinase (ERK) and the p38 mitogen-activated protein kinase (p38MAPK) were analysed by Western blotting using a phospho-specific antibody.ResultsTreatment of quiescent endothelial cells with HGF resulted in significant dose-dependent increases in cell numbers and decreases in lactate dehydrogenase (LDH) release. Moreover, HGF significantly attenuated endothelial cell death induced by culture in serum-free conditions. We therefore focused on the signal transduction system, and in particular on ERK and p38MAPK. ERK was markedly phosphorylated by HGF. The contribution of ERK to cell growth was supported by the observation that addition of PD98059, a specific inhibitor of MAPK kinase, significantly attenuated the increase in endothelial cell numbers induced by HGF, in a dose-dependent manner. Similarly, PD98059 also attenuated the decrease in LDH release and DNA fragmentation by HGF under serum-free conditions. Interestingly, ERK was re-phosphorylated at 12 h after stimulation. Re-phosphorylation of ERK was the result of induction of endogenous HGF by exogenously added HGF, as addition of neutralizing anti-HGF antibody to the conditioned medium attenuated re-phosphorylation of ERK at 12 h. In contrast, although p38MAPK was also phosphorylated by HGF, SB203580, a specific inhibitor of p38MAPK, failed to change the endothelial cell growth induced by HGF.ConclusionWe have demonstrated that the anti-apoptotic action of HGF against endothelial cell death was mainly through phosphorylation of ERK on human endothelial cells.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe relationship between low birth weight and elevated blood pressure in adult life is well established but presently unexplained. Both microvascular dysfunction and insulin resistance have been proposed as a possible explanation. We have examined the relation between birth weight and blood pressure in 30 healthy subjects exhibiting a wide range of insulin sensitivity, and assessed whether microvascular function and/or insulin resistance may underlie this relationship.MethodsBirth weight data were obtained from birth announcements. Blood pressure was measured with an ambulatory blood pressure monitor and insulin sensitivity was assessed by the hyperinsulinaemic, euglycaemic clamp technique. Microvascular function, i.e. capillary recruitment and endothelium-dependent and -independent vasodilatation in the skin, was evaluated by videomicroscopy and iontophoresis of acetylcholine and sodium nitroprusside.ResultsBirth weight was significantly associated with blood pressure (r=−0.50;P< 0.05), capillary recruitment (r= +0.52;P< 0.05), acetylcholine-mediated vasodilatation (r= +0.40;P< 0.05), insulin sensitivity (r= +0.62;P< 0.01) and waist-to-hip ratio (r= −0.42;P< 0.05). Regression analysis showed a significant association of birth weight with 24 h systolic blood pressure (regression coefficient: −7.6 mmHg/kg; 95% confidence interval: −13.0 to −1.0). Adjustment for capillary recruitment and waist-to-hip ratio decreased the regression coefficient by 39 and 41%, respectively. The results were similar after adjustment for age, sex or body mass index.ConclusionThese results suggest that capillary recruitment and body fat distribution may partly explain the relationship between birth weight and blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundLacidipine is a widely used calcium-channel blocker, which has both long-lasting antihypertensive activity and also antioxidant properties. Previous studies have demonstrated the ability of lacidipine to reduce the development of atherosclerotic lesions in several animal models.ObjectiveThe present study investigated the anti-atherosclerotic potential of lacidipine in the apoE-deficient mouse, an experimental model of atherosclerosis showing progressively complex and widespread lesions which closely resemble the inflammatory-fibrous plaques seen in humans.MethodsLacidipine was administered daily by gavage for 10 weeks at dose levels of 0 (control), 0.3, 1.0 and 3.0 mg/kg.ResultsLacidipine administration reduces the extension of atherosclerotic lesions in the aorta of the apoE-deficient mouse without affecting plasma lipid levels. We also show that apoE-deficient mice have four-fold higher values of the proatherogenic peptide, endothelin, compared with the wild-type C57BL/6 mouse and that lacidipine administration reduced, in a dose-dependent manner, the concentrations of plasma endothelin.ConclusionLacidipine has anti-atherogenic effects in the apoE-deficient mouse, and reduces plasma endothelin concentrations.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID