摘要:

Microalbuminuria (MA) is a well recognized marker of cardiovascular complications in hypertension, but whether MA can predict adverse outcome in this clinical condition is still a subject for debate. The fact that in hypertensive cohorts those patients who showed an increase in albumin excretion rate also manifested an increased incidence of morbid events indicates that the presence of MA in hypertension may carry an increased cardiovascular risk. However, the prognostic significance of MA remains controversial because no results of prospective studies performed in hypertensive subjects without diabetes mellitus are available. Several factors can affect the prevalence of MA in hypertension, including severity of the disease, selection procedures, concomitant risk factors, degree of obesity, age, and sex distribution. This accounts for the large differences in the prevalence of MA that can be found in the literature, with prevalence rates going from a low of 4.7% to a high of 40%. There is still conflict over whether MA in hypertension is due to increased intraglomerular pressure or to glomerular damage. The data from the literature suggest that in subjects with mild hypertension the main determinant of albumin excretion rate is the haemodynamic load. In subjects with more severe hypertension and hypertensive complications, the augmented urinary albumin leak is probably the consequence of a systemic microvascular disturbance which involves the glomeruli. In this respect, the insulin resistance state often associated to high blood pressure appears as one of the main pathogenetic factors. Whether management of hypertensive populations may be improved by monitoring of albumin excretion rate and whether antihypertensive drugs which are more effective in decreasing urinary albumin can be more beneficial in patients with MA remains to be determined.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesIn view of the critical role of intracellular Ca2+-overload in the genesis of myocyte dysfunction and the ability of reactive oxygen species (ROS) to induce the intracellular Ca2+-overload, this article is concerned with analysis of the existing literature with respect to the role of oxidative stress in different types of cardiovascular diseases.ObservationsOxidative stress in cardiac and vascular myocytes describes the injury caused to cells resulting from increased formation of ROS and/or decreased antioxidant reserve. The increase in the generation of ROS seems to be due to impaired mitochondrial reduction of molecular oxygen, secretion of ROS by white blood cells, endothelial dysfunction, auto-oxidation of catecholamines, as well as exposure to radiation or air pollution. On the other hand, depression in the antioxidant reserve, which serves as a defense mechanism in cardiac and vascular myocytes, appears to be due to the exhaustion and/or changes in gene expression. The deleterious effects of ROS are mainly due to abilities of ROS to produce changes in subcellular organelles, and induce intracellular Ca2+-overload. Although the cause–effect relationship of oxidative stress with any of the cardiovascular diseases still remains to be established, increased formation of ROS indicating the presence of oxidative stress has been observed in a wide variety of experimental and clinical conditions. Furthermore, antioxidant therapy has been shown to exert beneficial effects in hypertension, atherosclerosis, ischemic heart disease, cardiomyopathies and congestive heart failure.ConclusionsThe existing evidence support the view that oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases and that the antioxidant therapy may prove beneficial in combating these problems.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that sleep-related breathing disorder (SRBD) is associated with poor blood pressure control in hypertensive patients independent from confounding factors such as age, body mass index, alcohol, smoking and daytime blood gases.Design and methodsThis cross-sectional study of a sleep laboratory cohort was carried out at the University Hospital Sleep Disorders Centre, Marburg. The study comprised 599 patients referred for a sleep study, all of them with a documented history of systemic hypertension and/or previously initiated antihypertensive therapy. Data were obtained from a clinical interview, two unattended sleep studies and assessment of clinic blood pressure, cholesterol level, alcohol and nicotine consumption and daytime blood gases. The main outcome measure was a post hoc analysis of predictors for poor blood pressure control.ResultsRespiratory disturbance index (RDI) was significantly higher in patients with uncontrolled hypertension (blood pressure ⩾ 160 and/or 95 mmHg,n= 463) than in those with controlled hypertension (n= 136) (34.0 ± 26.8 versus 27.0 ± 23.5,P<0.01). The relative proportion of patients with uncontrolled hypertension increased significantly as SRBD activity increased (χ2,P<0.05). Body mass index was the only independent predictor (P= 0.006) of uncontrolled hypertension in the whole study sample. However, in the subset of patients aged ⩽ 50 years, RDI (P= 0.006) and age (P= 0.016) were the only independent predictors. The probability of uncontrolled hypertension increased by approximately 2% (B = 0.019,P= 0.006) for each RDI unit.ConclusionSRBD should be considered, in addition to traditional confounders, as a risk factor for poor blood pressure control in younger hypertensive patients (⩽ 50 years of age).

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe amino-terminal polymorphisms, Arg16Gly and Gln27Glu, of the β2-adrenergic receptor (β2AR) have been shown to affect regulation of the receptor expression by an agonist in cell culture studies. The Arg16Gly polymorphism has also been recently shown to be associated with essential hypertension. We therefore evaluated whether the amino-terminal polymorphisms of β2AR are associated with hypertension in a Caucasian population.Subjects and methodsWe performed an association study in 298 hypertensive patients and an equal number of age-matched normotensive controls from the East Anglian region, with blood pressure assessed categorically and quantitatively. We also examined the influence of the amino-terminal polymorphisms on blood pressure response to β-blockade in 144 of the patients randomly assigned to this class of drug. Genotyping of the Arg16Gly polymorphism was undertaken by a newly designed mismatched polymerase chain reaction (PCR) and digestion withNdeI, whereas the Gln27Glu polymorphism was genotyped by PCR followed byFnu4H I cleavage.ResultsWe found no differences in the genotype or allele frequencies of the β2AR polymorphisms between hypertensive and normotensive participants. There was also no association between the β2AR genotypes and variations in either basal blood pressure or the blood pressure response to a β-blocker.ConclusionThese findings suggest that the amino-terminal polymorphisms of the β2AR gene are unlikely to constitute major susceptibility for essential hypertension in the East Anglian population.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveFructose feeding induces hypertension, insulin-resistance and hypertriglyceridemia in Sprague-Dawley rats. The mechanisms of fructose-induced hypertension are as yet unknown. Here we investigate the effects of fructose feeding and of varying salt intake on blood pressure, glucose tolerance, plasma renin activity, and tissue angiotensinogen, renin, and AT1receptor mRNA levels in this model of hypertension.Design and methodsTo investigate the role of the renin-angiotensin system in fructose-induced hypertension we measured angiotensinogen, renin and angiotensin II type 1 (AT1) receptor mRNA levels in tissues of Sprague-Dawley rats that were fed either standard rat chow or a diet containing 66% fructose.ResultsBlood pressure (P<0.05) and triglyceride (P<0.01) levels were significantly greater in the fructosefed animals. Plasma glucose and insulin responses to an oral glucose load were significantly greater (P<0.05) in fructose-fed than control rats. Angiotensinogen mRNA levels in liver and fat, and renin mRNA levels in kidney did not differ between fructose-fed and control animals. Levels of AT1receptor mRNA were significantly greater in the fat obtained from fructose-fed rats than in that from control rats (P<0.05), but this was not so in the kidney. To determine whether fructose-induced hypertension is dependent on dietary salt content, rats were fed standard rat chow and a fructose-enriched diet with low and high sodium chloride concentrations. Blood pressure increased significantly (P<0.05) only in the fructose-fed rats receiving the high-salt diet. Similarly, increased AT1receptor mRNA levels were observed only in the fructosefed rats that were maintained on the high-salt diet.ConclusionsFructose feeding induces hypertension in normal- or high-salt fed animals and it is associated with an increased expression of the AT1receptor in adipose tissue. These findings suggest that AT1receptors might play a role in the pathophysiology of metabolic and hemodynamic abnormalities induced by fructose feeding.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo clarify ex-vivo polymorphonuclear leukocytes (PMNs) functions, we examined superoxide anion (O2−) production and adhesion to a plastic plate of isolated PMNs obtained from spontaneously hypertensive rats (SHR/Izm),NG-nitro-L-arginine methyl ester (L-NAME)- and deoxycorticosterone acetate (DOCA)/salt-induced hypertensive rats.DesignSixteen week-old male SHR/Izm and Wistar-Kyoto rats (WKY/Izm) were used as a model of hypertension and its control, respectively. L-NAME-hypertension was induced by oral administration of 100 mg/kg per day of L-NAME twice daily for 4 weeks using 4-week-old male Wistar rats. DOCA/salthypertension was induced by once daily subcutaneous injection of 1 mg DOCA with 1% NaCl drinking water for 2 weeks using 8-week-old male Wistar rats with heminephrectomy.MethodsHeparinized whole blood was obtained from abdominal aorta. PMNs were isolated by density gradient following dextran sedimentation. A production of superoxide anion (O2−) by PMNs stimulated with phorbol ester myristate acetate (PMA, 100 ng/ml) was determined by a superoxide dismutase (SOD)-inhibitable cytochrome-C reduction method. Adhesion of PMNs was evaluated by their protein content on a plastic plate measured by Lowry method.ResultsSHR/Izm showed a significant enhancement of O2−production by isolated PMNs compared with WKY/Izm. Rats treated with L-NAME showed a lower O2−production by PMNs compared to control animals. In DOCA/salt hypertensive rats, O2−production was not different from that in the control rats. Adherent function of isolated PMNs did not differ significantly among these hypertensive animal models.ConclusionsThese results suggest that O2−production by circulatory PMNs is augmented in SHR, but not in L-NAME and DOCA/salt hypertensive rats. This enhanced function, which is also observed in human essential hypertension, might contribute to the development of cardiovascular damage in genetically determined hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveLipoproteins and coagulation factors are independent predictors of atherothrombotic events in the general population and their interaction may contribute to the development of cardiovascular damage. This study was designed to assess relationships between lipoproteins, haemostatic variables, and atherosclerotic complications in hypertensive patients.MethodsIn 389 untreated essential hypertensive patients recruited at a hypertension clinic, we measured plasma lipids, apolipoproteins, lipoprotein (a), apolipoprotein (a) isoforms, fibrinogen, and parameters that directly reflect the coagulation activation. Hypertensive patients were compared to 92 normotensive controls.ResultsUnivariate analysis showed log lipoprotein (a) concentrations to be significantly correlated with age (P<0.02), apolipoprotein B (P<0.02), plasma fibrinogen (P<0.001), and fibrin D-dimer (P<0.001) levels, but not with body mass index, blood pressure, dietary fat intake, cholesterol, triglycerides, apolipoprotein AI, prothrombin fragment 1 + 2, and antithrombin III. The relationship of lipoprotein (a) with fibrinogen and D-dimer was present in both sexes, whereas the relationship of lipoprotein (a) with age and apolipoprotein B was found only in males. Multiple regression analysis showed that both fibrinogen and D-dimer were independently related with lipoprotein (a). Elevated fibrinogen, D-dimer, and lipoprotein (a) levels were significantly and independently associated with clinical evidence of atherosclerotic disease. To investigate whether the relationships of lipoprotein (a) with coagulation parameters are genetically determined, we analysed apolipoprotein (a) phenotypes in a subset of 188 hypertensive patients. While lipoprotein (a) levels were inversely correlated with apolipoprotein (a) isoform protein size, both fibrinogen and D-dimer concentrations were comparable in patients with apolipoprotein (a) isoforms of different size.ConclusionsThis study demonstrates a relationship between lipoprotein (a) and clotting variables in hypertensive patients that may contribute to atherosclerotic damage in these patients. There is no evidence of a genetic background for this relationship.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveWhether adrenaline acts as a sympathetic nervous cotransmitter in humans and stimulates β2-adrenoceptors to augment neuronal noradrenaline release remains a subject of considerable dispute. The aim of this study was to test if adrenaline is released from regional sympathetic nerves (in the heart) in patients with essential hypertension, and to investigate whether locally released adrenaline might enhance cardiac noradrenaline release.MethodsUsing dual isotope dilution methodology, adrenaline and noradrenaline plasma kinetics was measured for the whole body and in the heart in 13 untreated patients with essential hypertension and 27 healthy volunteers. All research participants underwent cardiac catheterization under resting conditions.ResultsAt rest, there was negligible adrenaline release from the sympathetic nerves of the heart in healthy subjects, 0.27 ± 1.62 ng/min. In contrast, in patients with essential hypertension, adrenaline was released from the heart at a rate of 1.46 ± 1.73 ng/min, equivalent on a molar basis to approximately 5% of the associated cardiac noradrenaline spillover value. Cardiac noradrenaline spillover was higher in hypertensive patients, 24.9 ± 17.0 ng/min compared to 15.4 ± 11.7 ng/min in healthy volunteers (P<0.05). Among patients, rates of cardiac adrenaline and noradrenaline spillover correlated directly (r= 0.59,P<0.05).ConclusionsThis study, in demonstrating release of adrenaline from the heart in patients with essential hypertension, and in disclosing a proportionality between rates of cardiac adrenaline and noradrenaline release, provides perhaps the most direct evidence to date in support of the ‘adrenaline hypothesis’ of essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe exact role of angiotensinogen (AGT) in vascular remodeling has yet to be determined. In the present study, we examined the effects of reducing plasma AGT by intravenous injections with antisense oligodeoxynucleotides (ODNs) against AGT targeted to the liver on vascular remodeling in spontaneously hypertensive rats (SHRs).Design and methodsThe ODNs against rat AGT were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for regulating liver gene expression. Male SHRs (n= 18) and age-matched male Wistar-Kyoto (WKY) rats (n= 4) were used for this study. All animals were fed a standard rat diet throughout the experiment. At 10 weeks of age, the SHRs were divided into three groups (n= 6); systolic blood pressure (SBP) was similar in each group. The control group received saline, the sense group was injected with the sense ODN complex and the antisense group was injected with the antisense ODN complex. WKY rats were fed for the same period of time. The ASOR-poly(L)lysine-ODN complex was injected into the tail veins twice a week.ResultsAt the end of the treatment, a reduction in AGT mRNA levels in the liver and plasma AGT was observed only in the animals injected with antisense ODNs. Antisense ODNs significantly reduced the plasma angiotensin II (Ang II) concentrations to levels similar to those observed in WKY rats. Antisense ODNs significantly reduced the SBP (180.7 ± 4.4 mmHg) and media cross-sectional areas of the aorta (1.11 ± 0.02 mm2), which were still larger than those seen in WKY rats (140.3 ± 2.1 mmHg, 0.84 ± 0.02 mm2), compared with the SHRs injected with sense ODNs (225.2 ± 4.4 mmHg, 1.24 ± 0.02 mm2) and control SHRs (223.7 ± 4.8 mmHg, 1.25 ± 0.02 mm2). The aortic angiotensin-converting enzyme (ACE) activity and collagen concentrations, which were significantly higher than those seen in WKY rats, did not significantly change among the SHR groups. The aortic AGT, ACE, angiotensin II type 1 (AT1) receptor and angiotensin II type 2 (AT2) receptor mRNA also did not significantly change among the SHR groups.ConclusionOn the basis of these findings, plasma AGT is thus considered to play a role in the development of hypertrophy of smooth muscle in the aorta of SHRs, it is thought to have only a slight effect, however, on the remodeling of the matrix tissue when the suppression of hypertension is insufficient.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID