摘要:

The endothelins are a family of endothelium-derived peptides that possess characteristically sustained vasoconstrictor properties. Endothelin-1 appears to be the predominant member of the family generated by vascular endothelial cells. In addition to its direct vascular effects, endothelin-1 has inotropic and mitogenic properties, influences homeostasis of salt and water, alters central and peripheral sympathetic activity and stimulates the renin–angiotensin–aldosterone system. Studies with endothelin receptor antagonists have indicated that endothelin-1 probably has complex opposing vascular effects mediated through vascular smooth muscle and endothelial ETAand ETBreceptors. Endogenous generation of endothelin-1 appears to contribute to maintenance of basal vascular tone and blood pressure through activation of vascular smooth muscle ETAreceptors. At the same time, endogenous endothelin-1 acts through endothelial ETBreceptors to stimulate formation of nitric oxide tonically and to oppose vasoconstriction.In view of the multiple cardiovascular actions of endothelin-1, there has been much interest in its contribution to the pathophysiology of hypertension. Results of most studies suggest that generation of, or sensitivity to, endothelin-1 is no greater in hypertensive than it is in normotensive subjects. Nonetheless, the deleterious vascular effects of endogenous endothelin-1 may be accentuated by reduced generation of nitric oxide caused by hypertensive endothelial dysfunction. It also appears likely that endothelin participates in the adverse cardiac and vascular remodelling of hypertension, as well as in hypertensive renal damage. Irrespective of whether vascular endothelin activity is increased in hypertension, anti-endothelin agents do produce vasodilatation and lower blood pressure in hypertensive humans. There is more persuasive evidence for increased endothelin-1 activity in secondary forms of hypertension, including pre-eclampsia and renal hypertension. Endothelin-1 also appears to play an important role in pulmonary hypertension, both primary and secondary to diseases such as chronic heart failure. The hypotensive effects of endothelin converting enzyme inhibitors and endothelin receptor antagonists should be useful in the treatment of hypertension and related diseases. Development of such agents will increase knowledge of the physiological and pathological roles of the endothelins, and should generate drugs with novel benefits.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo estimate hypertension's long-term cost and impact on life expectancy.DesignA 19-year individual follow-up study. Subjects were categorized according to their baseline (1972) diastolic blood pressure (DBP) level into three groups: normotensive (DBP < 95 mmHg), mildly hypertensive (DBP 95–104 mmHg), and severely hypertensive (DBP > 104 mmHg). By using their social security identification numbers, we linked the subjects to a set of national registers covering hospital admissions, use of major drugs, absence due to sickness, disability pensions, and deaths.SubjectsA random population sample of 10 284 men and women aged 25–59 years from the provinces of Kuopio and North Karelia in eastern Finland.Main outcome measuresThe numbers of years of life and years of work lost, the cost of drugs and hospitalization, and the value of productivity lost due to disability and premature mortality.ResultsThe difference in life expectancy between normotensive and severely hypertensive men was 2.7 years, of which 2.0 years was due to cardiovascular disease (CVD). Among women the corresponding differences were 2.0 and 1.5 years. Severely hypertensive men lost 2.6 years of work more than did normotensive men, of which 1.7 years was due to CVD. Among women the differences were 2.2 and 1.3 years. The mean undiscounted total costs (USA dollars at 1992 prices) were $132 500 among normotensive, $146 500 among mildly hypertensive, and $219 300 among severely hypertensive men, of which CVD accounted for 28, 39, and 43%, respectively. More than 90% of the total costs were indirect productivity losses. Among women the total costs were lower for all DBP categories, as were the shares of CVD-related costs. The proportional increase in costs on going from the lowest to the highest DBP category was, however, somewhat larger among women.ConclusionsOn the population level, severe hypertension leads to considerable losses in terms of years of life lost, years of work lost, and costs. However, the overall impact of mild hypertension is much more limited.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo assess the relationship between use of calcium antagonists and incidence of fatal or non-fatal cancer over 3 years in the Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly (STEPHY) population.DesignA prospective cohort study with follow-up analysis after 3 years.Patients and methodsIn 1992 STEPHY workers investigated the total population aged > 65 years (n= 1190) of two villages in Bavaria, Germany. With 982 participants (response rate 83%) the prevalence of ‘actual’ hypertension (blood pressure ≥ 160/95 mmHg or treatment) was 53%. Of all hypertensives (n= 491), 54% were being treated, 28% (n= 137) with calcium antagonists. Participants with a history of cancer or manifest cancer were excluded from further analysis. In 1995 in STEPHY II, the 3-year follow-up, we assessed total mortality (including cases of fatal cancer), cardiovascular events and cases of non-fatal cancer between 1992 and 1995. The evaluation included a second interview, use of case records of general practitioners and hospitals and analysis of the official death certificates. The total incidence of fatal and nonfatal cancer (a combined end point) was calculated for participants treated with calcium antagonists and those not taking calcium antagonists.ResultsTotal mortality over 3 years was 12.1% (n= 119). There were 22 deaths due to cancer and 75 cases of newly diagnosed non-fatal cancer. The combined incidence of fatal and non-fatal cancer (primary end point) was 10.9% (n= 15) for participants treated with calcium antagonists and 9.7% (n= 82) for those not taking calcium antagonists (odds ratio 1.12, 95% confidence interval 0.7–1.8). There was also no significant difference between the incidences of fatal cancer (2.2% in both groups), non-fatal cancer (12.5% for participants treated with calcium antagonists and 10.8% for those not taking calcium antagonists) and total mortality (14.6% for participants taking calcium antagonists and 11.7% for those not treated with calcium antagonists).ConclusionUse of calcium antagonists does not increase the risk of fatal or non-fatal cancer over 3 years in an elderly mid-European population.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these.DesignCross-sectional analyses at entry to a randomized controlled trial.SettingPatients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries.PatientsSix hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160–219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more.Main outcome measuresCognitive function tests (Reitan Trail Making A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest and Housework).ResultsPoor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index.ConclusionsAt entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare the limits of agreement between the SpaceLabs 90207 oscillometric blood pressure measurement device and the sphygmomanometer for patients with insulin-dependent diabetes mellitus (IDDM) versus healthy control subjects.DesignA retrospective analysis of six simultaneous blood pressure measurements in 106 IDDM patients aged 32.6 ± 12.0 years (mean ± SD) and 92 healthy control subjects aged 27.1 ± 8.9 years with the SpaceLabs device and a sphygmomanometer.ResultsFor both groups, overestimation of the systolic blood pressure occurred with the SpaceLabs device, being more severe for the IDDM group (1.7 mmHg more overestimation,P= 0.009). Mean arterial blood pressure was underestimated for the control group and overestimated for the IDDM group (2.7 mmHg underestimation and 0.8 mmHg overestimation, respectively). Diastolic blood pressures for both groups were underestimated by use of the SpaceLabs device, but less severely so for the IDDM group (4.2 mmHg,P< 0.0001 less underestimation). Multiple regression analysis revealed that these differences were mainly due to the presence of diabetes. Other determinants of these limits of agreement were age (for control group subjects) and duration of diabetes (for IDDM group patients).ConclusionLimits of agreement between the SpaceLabs 90207 device and the sphygmomanometer differ between IDDM patients and healthy controls. These limits are influenced by the presence of diabetes, age and duration of diabetes. Available protocols for the evaluation of automated blood pressure measurement devices of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation do not consider limits of agreement in subpopulations such as diabetic patients. Therefore, we recommend that tests for the limits of agreement of blood pressure measurement devices for subgroups should be added to these protocols.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLiddle's syndrome is an autosomal inheritable disorder that causes hypertension due to excess function of sodium channel.ObjectiveTo analyze the DNA sequence of the amiloride-sensitive epithelial sodium channel (ENaC) in three patients who had low-renin hypertension with hypokalemia. The patients included a 24-year-old woman and her 20-year-old brother whose mother was hypertensive. The third patient was a 15-year-old girl with no family history of hypertension.MethodsThe DNA sequence of the ENaC was analyzed as follows. Venous blood samples were collected from the patients and total genomic DNA was prepared by standard methods. Specific primers were used for direct polymerase chain reaction; one set of primers for amplifying the C terminus (codon 523–638) of the b subunit of ENaC, and two sets of primers for amplifying the C terminus (codons 525–587 and 568–650) of the γ subunit of ENaC. Polymerase chain reaction products were purified and subjected to direct DNA sequence analysis.ResultsDirect sequence analysis demonstrated the presence of a single-base substitution in one segment of the b subunit of ENaC, a C→T transition that changed the encoded Pro (CCC) at codon 616 to Ser (TCC) in the siblings (cases 1 and 2). In case 3, we found a missense mutation of Pro (CCC) to Leu (CTC) at codon 616. Case 3 is considered to be sporadic, since DNA sequencing of the PY motif of her parents gave normal results.ConclusionsThe DNA sequences of the ENaC in three patients with Liddle's syndrome were analyzed. In one family case, we found a new missense mutation of Pro (CCC) to Ser (TCC) at codon 616 in the β subunit of ENaC. A genetic analysis of the amiloride-sensitive epithelial sodium channel is recommended in assessing patients with low-renin, salt-sensitive hypertension whose blood pressure is not responsive to spironolactone treatment.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesTo compare the distributions of the genotypes and alleles of the M235T polymorphism of the angiotensinogen gene for hypertensive patients and normotensive controls.DesignA study of association of genetic polymorphisms.SettingAn outpatient clinic run by a university department handling referrals from primary care.PatientsTwo hundred and four subjects, 103 normal controls and 101 patients with newly diagnosed or documented hypertension.MethodGenomic DNA was extracted from peripheral blood leucocytes, amplified by polymerase chain reaction and digested with the restriction enzyme Tth 111 I. Methionine (M) and threonine (T) alleles were identified after electrophoresis.Main outcome measuresPrevalences of angiotensinogen genotypes and alleles for hypertensive patients and controls.ResultsMM, TM and TT genotypes occurred in 3, 24 and 73% of controls and 1, 22 and 77% of hypertensive patients, respectively. The prevalences of the M and T alleles were 0.15 and 0.85 among controls and 0.12 and 0.88 among hypertensive patients. The prevalences of the angiotensinogen genotypes and alleles for controls and hypertensive patients did not differ significantly.ConclusionsOur findings differed from previous reports and suggested that this polymorphism is not associated with hypertension in this population.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo investigate the role of the renin gene in the hypertension of the spontaneously hypertensive rat (SHR) of the Okamoto strain.MethodsWe determined whether the SHR renin allele was cosegregated with high blood pressure in 137 F2rats derived from inbred SHR and Wistar–Kyoto rats. Systolic blood pressure in conscious rats was measured by the tail-cuff method, whereas mean arterial pressure was determined from an indwelling catheter in the left carotid artery. Renin genotypes of F2rats were determined using a SHR-specificBglIIrestriction fragment length polymorphism that we have previously described.ResultsThe SHR renin allele was cosegregated significantly with higher systolic blood pressure in male F2rats aged 8–24 weeks and in females aged 12–24 weeks. The greatest differences in blood pressure between SHR renin allele homozygotes and Wistar–Kyoto rat renin allele homozygotes were 35 mmHg for males and 17 mmHg for females aged 24 weeks. The SHR renin allele was also associated with a higher mean arterial pressure in rats aged 24 weeks and cosegregated with higher body weight of male F2rats aged 12–24 weeks but not with that of the females. In contrast to the relationship with blood pressure, the SHR renin allele was segregated with lower plasma renin concentrations in rats aged 24 weeks.ConclusionThese results are consistent with the SHR renin gene being one of the loci determining high blood pressure in rats of this strain, possibly through action at some extra-renal site subserving control of blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID