摘要:

All components of the renin–angiotensin system (RAS) are highly expressed in the developing kidney in a pattern that suggests a role for angiotensin II in renal development. In support of this notion, pharmacological interruption of angiotensin II type-1 (AT1) receptor-mediated effects in animals with an ongoing nephrogenesis produces specific renal abnormalities characterized by papillary atrophy, abnormal wall thickening of intrarenal arterioles, tubular atrophy associated with expansion of the interstitium, and a marked impairment in urinary concentrating ability. Similar changes in renal morphology and function also develop in mice with targeted inactivation of the genes that encode angiotensinogen, angiotensin converting enzyme, or both AT1receptor isoforms simultaneously. Taken together, these results clearly indicate that an intact signalling through AT1receptors is a prerequisite for normal renal development. In a recent study, an increased incidence of congenital anomalies of the kidney and urinary tract was detected in mice deficient in the angiotensin II type-2 receptor, suggesting that this receptor subtype is also involved in the development of the genitourinary tract. The present report mainly reviews the renal abnormalities that have been induced by blocking the RAS pharmacologically or by gene targeting in experimental animal models. In addition, pathogenetic mechanisms and clinical implications are discussed.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThere have been very few studies on life prognosis of cardiovascular disease according to blood pressure stratifiation in the Japanese. Therefore, in Japan, although treatment of hypertension is possible, albeit at times difficult, due to the availability of various antihypertensive medications, the appropriate time at which treatment should be started remains a problem.ObjectiveTo investigate the long-term prognosis of cardiovascular disease in the Japanese general population according to blood pressure stratification in the Japanese.DesignA community-based prospective cohort study of 1996 men and women between the ages of 40 and 64 years at the baseline examination was conducted over an 18-year period. Information on death was obtained from local public health nurses and death certificates. The causes of death were clarified by questionnaires sent to doctors in the hospital in which the deceased was hospitalized, and the causes of death were analysed in each blood pressure category at baseline examination.ResultsMortality from cardiovascular disease increased with increases in the level of blood pressure and was significantly higher in ≥ 140 mmHg group in systolic blood pressure and ≥ 90 mmHg group in diastolic blood pressure, adjusted for age, sex and other cardiovascular risk factors in the Japanese general population. However, mortality risk from cardiovascular disease did not have a J-shaped relationship with systolic and diastolic blood pressure.ConclusionWe conclude that the optimum time for starting treatment in Japanese people is when blood pressure is 140/90 mmHg or less.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo describe the prevalence, detection, treatment and control of hypertension in an urban and rural area of Tanzania.DesignTwo linked cross-sectional population-based surveysSettingA middle-income urban district of Dar es Salaam (Ilala) and a village in the relatively prosperous rural area of Kilimanjaro (Shari)ParticipantsSeven hundred and seventy adults (> 15 years) in Ilala and 928 adults in Shari were studiedResultsHypertension prevalence (blood pressure >140 and/or 90 mmHg, or known hypertensives receiving antihypertensive treatment) was 30% (95% confidence interval, 25.1–34.9%) in men and 28.6% (24.3–32.9%) in women in Ilala, and 32.2% (27.7–6.7%) in men and 31.5% (27.8–35.2%) in women in Shari. Age-standardized hypertension (to the New World Population) prevalence was 37.3% (32.2–42.5%) among men and 39.1% (34.2–44.0%) in women in Illala, and 26.3% (22.4–30.4%) in men and 27.4% (24.4–30.4%) in women in Shari. In both areas, just under 20% of hypertensive subjects were aware of their diagnosis, approximately 10% reported receiving treatment and less than 1% were controlled (blood pressure < 140/90 mmHg). Hypertensive subjects were older, had greater body mass indices and waist: hip ratios, and had more risk factors for hypertension and its complications (smoking, heavy alcohol consumption, physical inactivity, obesity and diabetes) than nonhypertensives.ConclusionsThere is a high prevalence of hypertension in rural and urban areas of Tanzania, with low levels of detection, treatment and control. This demonstrates the need for cost-effective strategies for primary prevention, detection and treatment of hypertension and the growing public health challenge of non-communicable diseases in Sub-Saharan Africa.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveA growing body of research indicates that defensive personality styles (in particular, self-deception) may be related to higher resting blood pressure and stress reactivity levels. This study is the First, however, to examine the value of defensiveness as a prognostic indicator for the development of clinical hypertension.MethodsParticipants were 127 initially normotensive male and female adults who completed a comprehensive protocol including psychological testing, assessment of smoking, physical activity and body fat levels, and 8–12 h ambulatory blood pressure monitoring. Participants returned 3-years later for an identical follow-up protocol. Defensiveness was assessed using the Balanced Inventory of Desirable Responding.ResultsAt 3-year testing, 15 of 127 participants (12%) met criteria for hypertension (i.e. ambulatory mean blood pressure >140/90). Comparisons between defensiveness groups showed that 12 of 60 (20%) high defensiveness participants met hypertension criteria, whereas only three of 67 (4.5%) low defensiveness participants were hypertensive. Logistic regression equations adjusted for age, alcohol usage, bodyfat, self-reported exercise levels, smoking, and year-1 ambulatory blood pressure, revealed that membership in the high defensiveness group was associated with more than a sevenfold risk of 3-year hypertension (adjusted risk ratio, 7.5; 95% confidence interval, 1.5–39.2).ConclusionsThese findings link defensive characteristics to an increased prospective risk of hypertension using state of the art ambulatory monitoring techniques, and were robust after controlling for established risk factors. We conclude that the current results add to the hypertension literature by demonstrating associations between personality and clinically relevant blood pressure criteria.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr).Design and methodsAn SHRsp/SHRsr F2-intercross (n= 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment, the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT1breceptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included.ResultsThe endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F2descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype.ConclusionA candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo determine whether or not β2adrenoceptor polymorphism is a risk factor for the development of hypertension in a Black South African populationBackgroundAttenuated vasodilator responses to endogenous catecholamines may contribute to the aetiology of hypertension. Downregulation of β2adrenoreceptors (β2AR) following stimulation with agonists is determined in part by variation at the β2AR gene locus. The Glu27β2AR genotype results in attenuated downregulation compared with the wild-type Gln27receptor, whereas Gly16exhibits enhanced down-regulation compared to Arg16. Possible racial differences in the prevalence of the β2AR polymorphisms may be an explanation for the blunted responses to isoprenaline and the increased prevalence of hypertension in Black African populations.MethodsOne hundred and ninety-two unrelated hypertensives and 123 normotensives of Black South African origin were studied. Hypertensives were recruited from hospital hypertension clinics in the province of Gauteng and if on treatment, had a 2–4 week washout period before 24-h ambulatory blood pressure assessment. Normotensive controls were recruited from the same community.ResultsThere was no significant association between either the Arg–Gly16polymorphism or the Gln–Glu27polymorphism and hypertension status. Furthermore, in the hypertensives, no significant association was seen between β2AR genotype at either site and clinical bloodpressure, 24-h blood pressure or left ventricular mass. A significant association was seen between Arg16homozygotes and lower body mass index in hypertensives (P= 0.007) although this was not a primary end point. Interestingly, the Glu27polymorphism was much rarer in this population (allelic frequency 17%) compared to a Caucasian population.ConclusionThese data suggest that β2AR polymorphism is not a risk factor for hypertension per se in this defined population. The possibility that the decreased prevalence of Glu27in black South African populations explains blunted vasodilator responses to isoprenaline requires further study.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundA mutation in the gene for angiotensinogen, changing the leucine residue at position 10 to a phenylalanine (L10F), has been reported in a patient with proteinuric pre-eclampsia.In vitroenzymatic studies suggest this mutation would increase production of the vasoactive peptide, angiotensin IIin vivo, and therefore explain the etiology of the maternal hypertension.ObjectiveTo determine whether mutation of codon 10 of angiotensinogen is common in pre-eclampsia, and therefore likely to be involved in disease susceptibility.DesignWe collected a cohort of 32 women with ‘true’ pre-eclampsia. All were normotensive prior to the 20th week of pregnancy, developed blood pressures consistently above 140/90 mmHg and had proteinuria of greater than 300 mg/day during the third trimester. All had blood pressures that returned to normal within 1 month of delivery; 31 women were primigravida. Genomic DNA was isolated from their peripheral blood lymphocytes for genetic analyses.MethodsA polymerase chain reaction-restriction enzyme-based assay was devised to screen for mutation of codon 10 of the angiotensinogen gene. In addition, we determined the frequency of a threonine residue at position 235 in the angiotensinogen gene, given previous controversial (r)ndings of association of this polymorphism with disease.ConclusionsWe detected no mutation of codon 10 in angiotensinogen in any of the 32 women studied, indicating that this mutation is not commonly associated with proteinuric pre-eclampsia. Furthermore, there was no increased frequency of threonine 235 in the affected individuals studied compared with respective normotensive Caucasian-American and African-American populations.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction.DesignThe effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured.Methodsand results The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence ofCypridina luciferinanalog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant.ConclusionsThe acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo investigate the effect of chronic antioxidant treatments on the development of nitrate tolerance in spontaneously hypertensive (SHR) and normotensive Wistar–Kyoto (WKY) rats by evaluating (i) coronary vascular reactivity, (ii) lipid peroxidation (malondialdehyde), and (iii) peroxynitrite formation (3-nitrotyrosine).MethodsTolerance was induced in 16-week-old male SHR and WKY, by 4 days of continuous treatment with nitroglycerin patches. Two groups were orally pre-treated (2-weeks) with antioxidants:N-acetyl-L-cysteine (NAC) or melatonin. Effects of serotonin (5-HT) and sodium nitroprusside (SNP) perfusion were tested in isolated Langendorff-perfused hearts. 3-nitrotyrosine levels were measured in coronary sinus effluent and malondialdehyde in plasma.ResultsNitrate tolerance reduced SNP-induced dilation in both strains. This alteration was differently improved by antioxidants: melatonin was effective in SHR, whereas NAC was effective in WKY. Tolerance also reduced 5-HT-mediated vasodilation in WKY, which was reversed by both antioxidants. By contrast, nitrate tolerance enhanced the vasoconstriction to 5-HT in SHR and both antioxidants prevented this response. Furthermore, tolerance was associated with higher malondialdehyde levels in both strains and with higher 3-nitrotyrosine levels in SHR. These changes were reversed by both antioxidants.ConclusionsA participation of oxidative stress was suggested during nitrate tolerance development, since antioxidants prevented the increase in lipid peroxidation and improved vascular responses to SNP and 5HT. Differential effects of antioxidants on SNP-induced vasodilation in SHR and WKY may suggest distinct mechanisms of tolerance development in hearts from hypertensive and normotensive rats. An increased peroxynitrite generation, expressed by higher 3-nitrotyrosine levels, could contribute to nitrate tolerance in the coronary circulation of SHR.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background and objectiveThe European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the β-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBMmax), the mean maximum IMT of 12 standard carotid sites (Mmax) and the overall maximum IMT (Tmax). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline.MethodTo evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers.ResultsThe overall coefficient of reliability (R) was 0.859 for CBMmax, 0.872 for Mmaxand 0.794 for Tmax. The reliability for CBMmaxwas stable during the 13/4-year baseline period (R= 0.848 to 0.953) and was uniform among the 23 field centres (R= 0.798 to 0.926). Intra-and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866.ConclusionThe results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID