ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Renal sodium re-absorption is a closely regulated process serving to maintain both extracellular fluid volume and arterial blood pressure. Proteins participating in sodium re-absorption and its regulation are therefore important candidate proteins whose genes may contain sequence variation contributing to the inherited tendency for increased arterial blood pressure (essential hypertension). Important insight has come from rare forms of single–gene hypertension in human subjects and from polygenic animal models of genetic hypertension. Both indicate the primacy of altered renal function in the genesis of hypertension, and suggest that genes contributing to the disease are members of the subset of genes expressed in the kidney. This review examines evidence for abnormalities in renal sodium re-absorption in hypertension and focuses on the proximal tubule as a site of relevant dysfunction. Identification of the proteins participating in renal sodium re-absorption and its regulation, particularly those involved in the renal pressure-natriuresis mechanism, will allow gene cloning and sequencing which in turn may lead to the identification of novel gene sequence variation participating in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

AimHypertension is an established major risk factor underlying the epidemic of coronary and cardiovascular diseases in most developed countries, and it has been shown to be a public health problem in many developing countries since the 1970s. This review was carried out to illustrate the current situation with regard to blood pressure levels and the prevalence and management of hypertension in developing countries.MethodsA search for papers published in medical journals from 1991 to 1998 was performed using the MEDLINE database. A total of 40 articles were selected according to previously defined criteria.ResultsHypertension is a public health problem for most of the developing countries reviewed, and it is frequently associated with low levels of awareness, treatment and control. A positive association between the gross national product per capita and the prevalence of hypertension in developing countries is also evident.ConclusionsDifferences in methodology between national surveys make international comparisons difficult. Nevertheless, low-cost hypertension control programmes in developing countries are needed, along with development of the primary prevention of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo assess changes in blood pressure from childhood to adulthood and the ability to predict adult blood pressure.DesignLongitudinal study of a cohort of children with baseline data and a follow-up survey after 20 years.SettingEpidemiological survey of schoolchildren and subsequent inhabitants of Kaunas, a town in Lithuania.ParticipantsThe children came from 15 schools and accounted for 25% of all 12- and 13-year-old children born in 1964 in Kaunas. The frst survey (n= 1082) was carried out in 1977. The same population was re-examined in 1997 (n= 505). Data from 217 men and 288 women, who participated in both the first and the most recent surveys, is presented.Main outcome measuresSystolic and diastolic blood pressure at the age of 32–33 years.ResultsIn the 20 years between the two surveys blood pressure increased more in men than in women. Statistically significant correlation between childhood and adult blood pressure levels was estimated (for systolic blood pressurer= 0.40 in men andr= 0.24 in women; for diastolic blood pressurer= 0.14 in men andr= .34 in women). Stepwise regression analysis of the data showed that the best predictors of adult blood pressure were the initial childhood blood pressure levels and change in BMI during the 20-year period for both men and women. Other factors were less predictive.ConclusionsChildhood blood pressure is related to adult levels and, together with changes in body mass index, is a significant predictor of adult blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the hypothesis that repeated arousals at the termination of apnea/hypopnea in obstructive sleep apnea syndrome (OSAS) are related to abnormal circadian rhythm of blood pressure (BP).Design and methodsWe performed polysomnography (PSG) with pulse oximetry in 26 middle-aged patients with OSAS aged 42–58 years (mean age 51.8 years). The intensity of arousal on PSG was graded into two levels: grade 1 (EEG arousal, EA), an abrupt shift in EEG frequency, and grade 2 (movement arousal, MA), EEG arousal with an increase in electromyogram activity lasting at least 3 s. The number of apnea/hypopneas per hour (apnea/hypopnea index, AHI), and length of time during which nocturnal oxygen saturation decreased below 90% (oxygen desaturation time, ODT) were also evaluated. Percentage EA and %MA were assessed by the ratio of the number of apneas and hypopneas with EA or MA to the number of apneas and hypopneas in total. The 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively. Multiple regression analysis was performed among AHI, ODT, %EA and %MA or among age, body mass index and %MA.ResultsThe %MA was the most significant factor contributing to the elevated 24 h SBP (r= 0.46,P<0.05); oxygen desaturation (r= 0.44,P<0.05) was the next most important contributing factor. The level and pattern of 24 h BP differed significantly between the patients with %MA 85% and %MA <85% (mean 24 h SBP: 147 ± 16.8 versus 125 ± 19.6 mmHg,P<0.01; mean 24 h DBP: 97.5 ± 14.3 versus 85.6 ± 14.6 mmHg,P<0.01), and also differed between those with severe OSAS, i.e. ODT >130 min, and mild to moderate OSAS, i.e. ODT <130 min, (mean 24 h SBP: 149 ± 15.8 versus 132 ± 20.6 mmHg,P<0.01; mean 24 h DBP: 100 ± 14.1 versus 87.4 ± 14.0 mmHg,P<0.01).ConclusionOur findings suggest that MA and oxygen desaturation in OSAS make an important contribution to abnormal circadian rhythm of BP. We conclude that repeated end-apneic arousal and/or hypoxic asphyxia and the subsequent sleep fragmentation may contibute to nocturnal and diurnal elevation of BP.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveStress has been shown to be a major environmental contributor to cardiovascular diseases through its effects on blood pressure variability and cardiac function. The cellular stress response is characterized by the expression of specific heat stress genes (hsps), under the transcriptional control of heat shock transcription factors (HSTFs). The levels ofhspmRNA depend on the severity of the stress, withhstf1acting as a stress sensor. The aim of this work was to evaluate the genetic contribution of the variability inhspexpression, and to identify its putative quantitative trait loci (QTL).MethodsTwenty recombinant inbred rat strains (RIS) were studied. The animals underwent a standardized, identical 1 h immobilization stress in restraint cages, followed by 1 h of rest before sacrifice. Total RNA was extracted from the heart, kidneys and adrenals, and the mRNA levels ofhsp27, hsp70, hsp84, hsp86andhsp105were measured. The strain distribution pattern (SDP) ofhspexpression was correlated with that of 475 polymorphic markers distributed throughout the RIS genome. A polymorphism of rathstf1in RIS was used for its mapping in RIS.ResultsDespite an identical stress being applied to all strains,hspexpression showed up to a 12-fold gradient with little intra-strain variability, indicative of a strong genetic contribution to the trait. Heritability ranged from 50 to 77% for mosthspgenes in the three target organs. The continuous SDP of stress gene expression indicated the polygenic nature of the trait. A common locus on chromosome 7 (atD7Cebrp187s3marker) was consistently associated with allhspexpression in most of the organs [with a likelihood of odds (LOD) score of 3.0 forhsp27expression]. We have mapped rathstf1on chromosome 7 at the same locus. Finally, theD4Mit19marker was significantly associated withhsp84expression in the heart (LOD score of 3.1).ConclusionTwo loci were linked with the differential expression of HSPs in response to immobilization stress in target organs of RIS. The chromosome 7 locus unveiled for all HSPs could explain up to 42% of the observed interstrain variability ofhsplevels in response to stress. We propose hstf1 as a positional candidate at this locus.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the hypothesis that the genotype at nucleotide A(−20)C in the 5′ flanking region of the angiotensinogen gene, which lies within a sequence with high homology to an oestrogen response element, affects plasma angiotensinogen levels in pregnancy.DesignProspective observational studyMethodsSeventy-two healthy pregnant women were recruited in the second half of pregnancy from hospital and primary care antenatal clinics in Nottingham, UK. Plasma angiotensinogen concentrations were measured by radioimmunoassay of angiotensin I generated from endogenous angiotensinogen in the presence of excess human renin. DNA was extracted from peripheral venous blood, and angiotensinogen genotype determined at A(−20)C, G(−6)A and Met235Thr. Associations between genotype and plasma angiotensinogen concentration were assessed by analysis of variance.ResultsWomen homozygous for the −20C allele had the lowest mean plasma angiotensinogen concentration of 1.7 ± 0.3 μmol/l. Women homozygous for −20A had significantly higher plasma angiotensinogen concentrations (2.6 ± 0.1 μmol/l), and intermediate levels (2.0 ± 0.1 μmol/l) were observed in women heterozygous for A(−20)C (P= 0.002, ANOVA). The polymorphisms at nucleotide −6 and codon 235 were in almost complete linkage disequilibrium, and nucleotide −20C was found only in a subset of −6 A/235Thr alleles.ConclusionThe low plasma angiotensinogen levels associated with the −20C/-6A/235Thr haplotype in pregnant women contrast with the high concentrations associated with the 235Thr allele in the non-pregnant state. A possible explanation lies in the presence of a motif with high homology to an oestrogen response element between the TATA box and transcription initiation site. Previousin vitrostudies of reporter gene constructs have demonstrated that the A(−20)C polymorphism affects oestrogen responsiveness. The results of this study support the hypothesis that the oestrogen response element of the angiotensinogen gene is of functional importance in pregnancy, and that oestrogen responsiveness in pregnancy is influenced by the genotype at nucleotide −20.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo compare the muscle morphology in hypertensive subjects with that in controls and to test the hypothesis of a relation between heart rate, development of hypertension and muscle morphology that is independent of glucose intolerance.Patients and methodsWe studied 43 glucose-tolerant, untreated hypertensive subjects and 113 healthy controls in a longitudinal cohort of 70-year-old men. Metabolic status (oral glucose tolerance test and euglycemic, hyperinsulinaemic clamp test), muscle fibre distribution (myosin ATPase staining) and capillary supply (amylase-PAS method) were evaluated. Blood pressure and heart rate data were available from both ages 50 and 70 years.ResultsHypertensive subjects had a significantly smaller mean number of capillaries per fibre than controls (1.53 versus 1.64;P= 0.04). In hypertensive subjects, the proportions of type I and type II fibres were correlated to mean arterial pressure (r= −0.56 andr= 0.52, respectively,P<0.05 for both). The increase in mean arterial pressure over 20 years was closely correlated to capillary density in mm2(r= −0.62;P<0.0001). Capillary supply was inversely related to resting heart rate both at ages 50 and 70 years.ConclusionsSkeletal muscle of glucose tolerant hypertensive subjects showed a lower capillary supply than that of controls. This capillary rarefaction was correlated to increase in mean arterial pressure over two decades and to supine heart rate. This is compatible with the suggestion that higher sympathetic drive might generate structural alterations in muscle capillarization.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background and objectivesIn spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+channels and increasing cytosolic free calcium and blood pressure. The thiol compound,N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, α-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs.Methods and resultsStarting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar-Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys.ConclusionsDietary α-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveExcess oxidative stress is one of the major metabolic abnormalities on vascular walls in hypertension and atherosclerosis. In order to further elucidate the endothelial function under oxidative stress, the effect of hydrogen peroxide (H2O2) on expression of two novel endothelium-derived vasorelaxing peptides, C-type natriuretic peptide (CNP) and adrenomedullin (AM) from bovine carotid artery endothelial cells (BCAECs) was examined.MethodsBCAECs were treated with H2O2(0.1-1.0 mmol/l) and/or an antioxidant, N-acetylcysteine (NAC) (5–10 mmol/l), and incubated for 48 h. The concentrations of CNP and AM were measured with the specific radioimmun assays that we originally developed. CNP and AM mRNA expressions were also examined by reverse transcription-polymerase chain reaction (RT-PCR).ResultsTreatment of BCAECs with 0.5 and 1 mmol/l H2O2induced 9-and 10-fold increases of CNP concentration in the media. Addition of 10 mmol/l NAC significantly suppressed the effect of H2O2by 52%. RT-PCR analysis showed that CNP mRNA expression in BCAECs was also rapidly augmented within 1 h with H2O2(1 mmol/l) treatment, and reached a peak at 3 h to show a 10-fold increase. AM secretion from BCAECs also increased to two-fold with exposure to 0.5 mmol/l H2O2, accompanied with the augmented level of AM mRNA. NAC 10 mmol/l completely suppressed the effect of H2O2on AM secretion.ConclusionsIn this study, it has been demonstrated that H2O2augments endothelial secretion of the two endothelium-derived relaxing peptides, CNP and AM. Our findings suggest the increased secretion of CNP and AM from endothelium under oxidative stress may function to compensate the impaired nitric oxide-dependent vasorelaxation in hypertension and atherosclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID