摘要:

The atrial natriuretic peptide (ANP), a component of the natriuretic peptide family, was discovered in 1981 when de Bold and his coworkers observed a natriuretic effect induced by infusion of atrial extracts in rats. Subsequently, an impressive amount of research has been carried out in order to identify the structure of the active peptide and its receptors, to characterize the biological functions of ANP and its involvement in the pathophysiology of diseases and, finally, its direct contributory role in the pathogenesis of some cardiovascular disorders. ANP plays a key role in the regulation of salt and water balance, as well as of blood pressure homeostasis. In addition, ANP is involved in the pathophysiology of hypertension and heart failure, and exerts a cellular antiproliferative effect in the cardiovascular system. More recently, a direct contributory role of ANP in the development of hypertension and of cerebrovascular disorders has been suggested by the use of molecular genetic approaches. Therefore, our understanding of the pathophysiologic relevance of ANP has changed over time, finally leading to the identification of ANP as a potential determinant of cardiovascular diseases, rather than as a simple marker of cardiac and vascular dysfunctions. This novel view of ANP may open interesting research pathways.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo define the prevalence of cardiovascular risk factors and their relation to the level of blood pressure, in Egyptians.MethodsData were collected during the Egyptian National Hypertension project, a national hypertension survey in Egypt. During phase I of the survey, hypertensive (HT) patients were identified. In phase II, clinical and laboratory evaluations were made on HT and gender-matched normotensives (NT). A total of 2313 individuals were examined, 311 NT males, 443 NT females, 670 HT males and 889 HT females.ResultsThe prevalence of obesity was 33 and 47% in hypertensive men and women, respectively. After adjusting for age, HT men had significantly higher heart rate, total cholesterol (TC), triglycerides (TG), fasting blood sugar (FBS), post-prandial blood sugar (PBS), body mass index and waist/hip (W/H) ratio than their NT counterparts. In addition, HT women had higher low-density lipoprotein cholesterol (LDL-C). The prevalence of elevated LDL-C and FBS increased with age. The prevalence of hypertriglyceridemia, elevated FBS and obesity rose with increasing level of blood pressure (BP). From the 25–34 to the 55–64 age group, the percentage of hypertensives with⩾2 risk factors rose from 42.9 to 60.6% in men, and from 9.4 to 46.2% in women. All risk factors were more prevalent in urban populations.ConclusionThis is one of the few reports on the prevalence of cardiovascular risk factors in a developing country. Risk factors cluster with rising level of BP and with ageing. Obesity is very prevalent, particularly in hypertensive Egyptian women. Health efforts directed at the prevention and treatment of obesity should be a high priority.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesEndothelium-derived nitric oxide plays a key role in the regulation of vascular tone. Recently, endothelial nitric oxide synthase (eNOS) gene polymorphisms were reported to be associated with hypertension or coronary spasm. We investigated the association between the eNOS gene polymorphisms and hypertension in a large population-based sample of 4055 Japanese.Design and methodsWe investigated two polymorphisms of the eNOS gene, Glu298Asp polymorphism of exon 7 and T(−786)C polymorphism of the promoter region. The genotype distribution in hypertensive subjects was compared to that in the other subjects. The influence of the genotype on blood pressure values was analyzed in the subjects not taking hypertensive medication. The promoter activities of the eNOS gene with the (−786)T or (−786)C allele were measured by a luciferase reporter gene assay.ResultsThere was significant linkage disequilibrium between the two polymorphisms (P< 0.0001). The genotype distribution of the Glu298Asp or T(−786)C polymorphism did not differ between the hypertensive and the other subjects. No significant differences in the blood pressure of subjects not taking hypertensive medication were observed among the three genotypes of Glu298Asp or T(−786)C polymorphisms. No significant differences in the promoter activity were observed between bovine endothelial cells transfected with the (−786)T and (−786)C alleles.ConclusionsOur data suggested that these polymorphisms of the eNOS gene are unlikely to be major factors in the susceptibility to hypertension in the Japanese population studied.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the relationship between angiotensinogen (ANG) genotype and blood pressure response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. The angiotensin converting enzyme (ACE) gene was also tested.DesignThe DASH trial was a randomized outpatient feeding study comparing the effects on blood pressure (BP) of three dietary patterns: a control diet, similar to typical American intake; a ‘fruits and vegetables’ diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and the DASH diet that is reduced in fats and that emphasizes fruits, vegetables and low-fat dairy products. Participants’ genotype was also determined.SettingFour clinical sites.ParticipantsAdults with above-optimal BP or stage 1 hypertension.InterventionParticipants ate one of the three dietary patterns for 8 weeks. Sodium intake and weight were held constant. In 355 of 459 DASH participants, DNA was extracted from leukocytes and genotyped for the G−6A ANG polymorphism and the D/I ACE polymorphism, by the polymerase chain reaction.Main outcomesGenotype at ANG and ACE loci; BP after 8 weeks of intervention diet.ResultsThere was no association between ACE genotype and BP response. Associations with ANG polymorphismwere significant: net systolic and diastolic BP response to the DASH diet was greatest in individuals with the AA genotype (−6.93/−3.68 mmHg) and least in those with the GG genotype (−2.80/0.20 mmHg). A similar relationship existed for the F/V diet.ConclusionsANG genotype is associated with BP response to the DASH diet. The AA genotype confers excess risk of hypertension and is associated with increased responsiveness to diet.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundFamilial hyperkalaemic hypertension (FHH) is a Mendelian form of low-renin hypertension characterized by hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate. To date, three different loci have been identified, on chromosomes 1, 17 and 12.ObjectiveTo test for genetic linkage between the three FHH loci and three new affected kindreds.Design and methodsClinical, biological and genetic analyses were made of three kindreds, including 11 affected individuals among 25 members. Genotyping was performed using four series of microsatellite markers spanning the chromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na–Cl cotransporter (SLC12A3) gene.ResultsSegregation of the trait in each kindred was compatible with an autosomal transmission, the affected individuals displaying reasonably consistent biochemical abnormalities and the expected variability in arterial hypertension. Multipoint linkage analysis excluded linkage with the four candidate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindred 3.ConclusionThese results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. They suggest a variety of molecular defects leading to FHH.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundSympathetic hyperactivity is observed in several disease states and may contribute to cardiovascular hypertrophic remodeling. Endothelin has been suggested to be a mediator of hypertrophy.ObjectiveTo examine the involvement of endothelin in maintaining the growth response induced by exogenous norepinephrine.Design and methodsRats were treated with norepinephrine (2.5 μg/Kg per min subcutaneously) for 2 and 4 weeks, alone or in association with the selective endothelin-A (ETA) receptor antagonist, darusentan (LU135252, 30 mg/Kg per day orally) for weeks 3 and 4.ResultsIncreases in medial cell number and accumulation of collagen and elastin characterized norepinephrine-induced aortic remodeling. These effects occurred without marked changes of mean arterial pressure, but may be related to enhanced pressure variability in addition to direct effects of norepinephrine. Inhibition of ETAreceptors by darusentan reversed aortic alterations produced by infusion of norepinephrine. Evaluation of medial apoptosis did not reveal any significant change in any group at 4 weeks.ConclusionsAntagonism of ETAreceptors effectively and rapidly reversed norepinephrine-induced aortic structural and compositional changes, suggesting a central role of endothelin in mediating this response. Thus, ETAreceptor antagonists may help to regress large artery remodeling in conditions of increased circulating catecholamine concentrations.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundSeveral studies have reported that the circulating concentration of hepatocyte growth factor (HGF) was increased in individuals with clinically overt atherosclerotic disease, including coronary heart disease and peripheral arterial disease. However, whether changes in the circulating concentration of HGF are associated with early atherosclerotic changes in apparently healthy individuals remains to be determined.ObjectiveTo investigate the relationship between the plasma concentration of HGF and carotid arterial remodeling.MethodsPlasma concentrations of HGF were measured in 201 community-dwelling healthy residents free from any medications and signs and history of cardiovascular disease. Carotid intima–media thickness (IMT) and carotid internal diameter were determined by ultrasonography with a 7.5 MHz probe. The study participants were divided into four groups according to the presence or absence of carotid atherosclerosis (presence of plaque, IMT⩾0.85 mm) and carotid arterial dilatation (diameter⩾7.0 mm).ResultsCarotid arterial remodeling, atherosclerosis or dilatation, or combinations thereof, was associated with significantly greater concentrations of plasma HGF. Among risk factors, plasma HGF was significantly associated with advanced age (⩾65 years), current smoking and diabetes mellitus, whereas sex, obesity, hypertension and hypercholesterolemia did not affect plasma concentrations of HGF. Multiple regression analysis showed that plasma HGF was independently associated with carotid arterial remodeling (atherosclerosis, dilatation, or both) in addition to age and systolic blood pressure.ConclusionsThese results indicate that the plasma concentration of HGF increases in relation to carotid arterial remodeling, independently of known risk factors for atherosclerosis. These findings further support a possible role of HGF in atherosclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundBaseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima–media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability.Methods and resultsIn 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2±7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day–night or clinic–day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P< 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values.ConclusionsThis is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundTwo distinct types of angiotensin II (AngII) receptors, AT1and AT2, have been cloned. We have shown previously that stimulation of AT2reduces intracellular cyclic guanosine monophosphate (cGMP) levels in cultured porcine chromaffin cells in which AT2is the predominantly expressed receptor. However, it has not been determined whether AT1or AT2affects signal transduction pathways involving mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) in chromaffin cells. Also, it is unclear whether cGMP/protein kinase G (PKG) is involved in the regulation of MAPKs and STATs in these cells.DesignChromaffin cells were derived from porcine adrenal medulla. The effects of AngII alone (representing physiological conditions), AngII plus CV-11974 (an AT1antagonist, which simulates specific AT2stimulation), AngII plus PD 123319 (an AT2antagonist, which simulates specific AT1stimulation), and 8-Br-cGMP (a membrane-permeable cGMP analogue) alone on MAPKs (ERKs, JNK, p-38 MAPK) and STATs (STATs 1, 3 and 5) activity were measured.MethodsPhosphorylated MAPKs (extracellular signal-related kinases (ERKs), c-jun N-terminal kinase (JNK) and p38 MAPK) and STATs (STATs 1, 3 and 5) were measured by immunoprecipitation–Western blot analysis (IP–Western blot).ResultsAT1stimulation markedly increased expression of ERKs, JNK, p38 MAPK via Ca2+-dependent protein kinase C (PKC) isoforms (cPKC), as well as STATs 1, 3 and 5 in cultured porcine chromaffin cells. In contrast, AT2stimulation markedly decreased the expression of these signaling molecules. Also, 8-Br-cGMP alone induced increases in ERKs, JNK, p38 MAPK, and STATs 1, 3 and 5. Because AT2inhibits cGMP production, we speculate that AT2may act to suppress cGMP production, which in turn reduces the activity of both MAPKs and STATs in chromaffin cells.ConclusionAT2negatively regulates AT1in signal transduction pathways in chromaffin cells.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundIt has been clearly demonstrated that angiotensin(1–7) potentiates the vasodilating effect of bradykinin in isolated vessels of animals.ObjectiveTo investigate the interaction between angiotensin(1–7) Ang(1–7) and bradykinin in human forearm resistant vessels of normotensive healthy menin vivo, by the measurement of forearm blood flow using venous occlusion, strain-gauge plethysmography with intra-arterial infusions of peptides in a placebo-controlled, double-blind, cross-over design.MethodsIn eight men, bradykinin was infused intra-arterially twice; placebo, Ang(1–7), or angiotensin II was co-infused with the second infusion. The effect of inhibition of nitric oxide synthase on the interaction between Ang(1–7) and bradykinin was also tested in eight other individuals. The effects of Ang(1–7) were analyzed by analysis of variance (ANOVA) and by the ratios of individually derived areas under the dose–response curves (AUC) of bradykinin, adjusted for changes in the AUCs by repeated infusions of bradykinin with placebo.ResultsAng(1–7) (1000 pmol/min) significantly potentiated the vasodilating effect of bradykinin compared with the effect of saline (P= 0.0471, ANOVA) and in a dose-dependent manner (adjusted AUC ratio [95% confidence interval (CI)] 2.75 (1.72 to 3.78) with 1000 pmol/min, 1.62 (1.31 to 1.93) with 100 pmol/min, and 0.98 (0.80, to 1.09) with 10 pmol/min). This effect was completely abolished by co-infusion ofNG-monomethyl-l-arginine [AUC ratio 0.98 (0.90 to 1.04)]. Ang(1–7) did not affect the vasodilating effects of either acetylcholine or sodium nitroprusside.ConclusionsAng(1–7) potentiates the vasodilating effect of bradykinin, possibly through a mechanism(s) involving nitric oxide release, in human forearm resistance vessels.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID