摘要:

Backgroundα-adducin is a cytoskeletal protein involved with sodium-pump activity in the renal tubule. The α-adducin gene locus has been linked to hypertension and a polymorphism identified which is associated with hypertension; however, the role of the α-adducin gene locus in normal blood pressure regulation is not defined. We performed a combined linkage and association study in normotensive monozygotic (MZ) and dizygotic (DZ) twins and their parents to address this issue.MethodsWe studied 126 MZ and 70 DZ twin pairs and parents of DZ twins. Blood pressure values and responses to a cold pressor test were obtained. Cardiac dimensions were measured echocardiographically. Three microsatellites adjacent to the α-adducin gene were studied as well as the 460 Trp mutation in the α-adducin gene.ResultsWe obtained strong evidence for linkage (P< 0.001) between the α-adducin gene locus and systolic blood pressure. However, we were not able to associate the 460 Trp mutation with higher blood pressures, cold pressor responses or cardiac dimensions.ConclusionsThe α-adducin gene locus is relevant to blood pressure regulation in normal subjects. Failure to find an association between higher blood pressures and the 460 Trp mutation suggests that this mutation may become important only when hypertension is triggered, or that other variations in α-adducin are present which have not yet been discovered.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveIn a conscious unrestrained rat model, it takes approximately 1 week for angiotensin II to increase blood pressure to maximum levels. We investigated the time required for hypertension to fully recover after acute angiotensin II receptor blockade in this angiotensin II dependent hypertensive model.DesignConscious unrestrained rats (n= 8) infused with 10 ng/kg per min angiotensin II for 21 days received losartan (10 mg/kg) on day 17 of angiotensin II infusion. Mean arterial pressure (MAP) and heart rate were monitored continuously. The acute pressor response to 50 ng/kg per min angiotensin II was monitored for 2 h on days 15, 17, 18, 19 and 20 of angiotensin II infusion. Plasma renin concentration (PRC) was measured daily.ResultsAngiotensin II increased MAP acutely by 26 ± 2 mmHg and by a further 23 ± 4 mmHg between days 4 and 8. Losartan acutely reduced MAP by 75 ± 2 mmHg; 24 h later MAP had partially recovered but remained suppressed by 47 ± 3 mmHg. MAP had not fully recovered 4 days later. Some 2 h after losartan, the acute pressor response to angiotensin II had fallen from 24 ± 2 mmHg to zero. This recovered to 13 ± 5 and 28 ± 2 mmHg 24 and 48 h post losartan. After losartan PRC rose from 0.1 ± 0.05 to above 1 ng/ml per h for less than 24 h.ConclusionA single dose of losartan reverses both the fast and slow pressor effects of continuous angiotensin II infusions. While losartan is metabolized, the fast vasoconstrictor effect recovers quickly but the slow pressor effect takes almost a week to build up again to maximum levels. Since the slow pressor effect is mediated via the AT1receptor, any means of blocking the renin–angiotensin system is likely to keep blood pressure below maximum hypertensive levels for several days after the drug has disappeared from the circulation.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo examine the relationship between leptin and insulin serum levels and systolic and diastolic blood pressure in young men.SettingKobe University of Mercantile Marine, Kobe, Japan.ParticipantsOne hundred and ninety-eight male students aged 18–20 years (comprising 100% of those eligible).Design and measurementsA cross-sectional survey of a sample of male college students was performed, with measurements to include anthropometry, blood pressure and blood tests after overnight fasting.ResultsCompared with 90 men with an optimal blood pressure, 56 men with high-normal and high blood pressure had an increase in body mass index (23.7 ± 5.2 versus 20.4 ± 2.2 kg/m2), percentage body fat (21.7 ± 8.0 versus 16.3 ± 4.2%) and serum leptin (3.7 ± 4.7 versus 1.5 ± 0.8 ng/ml). In addition, they had greater serum insulin (59 ± 31 versus 43 ± 12 pmol/l) despite there being no differences in plasma glucose, resulting in a reduction of the ratio of glucose to insulin (× 106) (107 ± 43 versus 126 ± 35), which is an estimate of insulin sensitivity in a nondiabetic population. Furthermore, the 56 men had higher serum triglyceride levels, although there was no difference in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol between men with optimal and high-normal plus high blood pressure. Similar differences were found between men in a top versus low tertile of systolic and diastolic blood pressure. In multiple regression analysis, both log leptin and log insulin emerged as determinants for systolic blood pressure independent of body mass index and percentage body fat, but an association with diastolic blood pressure was only shown for log leptin.ConclusionHyperleptinemia and hyperinsulinemia may be regulators of arterial pressure, independent of body mass index or percentage body fat.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveRecently, a novel C825T polymorphism in the gene (GNB3) encoding for the G-protein β3 subunit was identified. The 825T allele is associated with the generation of a novel splice variant, enhanced intracellular signal transduction, and arterial hypertension. In this study, we investigated the impact of the 825T allele on left ventricular structure and function in mild to moderate essential hypertensive subjects.MethodsIn 34 white patients with established mild to moderate essential hypertension (World Health Organization stage I or II, mean age 52 ± 9 years) genotype analysis of GNB3 C825T polymorphism, insertion/deletion polymorphism of the ACE gene and 1166 A/C polymorphism of the AT1receptor gene was performed. In each patient, 24 h ambulatory blood pressure measurement (SpaceLabs 90207) and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed.ResultsIn our homogenous study group, the GNB3 825T allele was not associated with casual and 24 h ambulatory blood pressure (CC versus TC/TT: 144 ± 13/92 ± 8 versus 151 ± 14/97 ± 7 and 143 ± 11/92 ± 7 versus 150 ± 16/96 ± 9 mmHg, respectively) or parameters of left ventricular structure (relative wall thickness: CC versus TC/TT, 0.48 ± 0.1 versus 0.46 ± 0.1; left ventricular mass: CC versus TC/TT, 281 ± 65 versus 299 ± 80 g). However, transmitral flow variables reflecting left ventricular diastolic filling were impaired in patients expressing the TC/TT genotype (ratio of peak late (A) to early (E) velocities: CC versus TC/TT, 0.95 ± 0.24 versus 1.2 ± 0.26,P< 0.02; velocity time integrals A/E: CC versus TC/TT, 0.57 ± 0.16 versus 0.76 ± 0.23,P< 0.01) while all co-variables such as age, body mass index, ambulatory blood pressure, heart rate and end-diastolic volume were similar between the two groups. If patients were stratified according to the I/D polymorphism of the ACE gene and the A1166C polymorphism of the AT1receptor gene, no differences in blood pressure, left ventricular structure or systolic and diastolic function of the left ventricle were found between different genotypes.ConclusionThe GNB3 825T allele was associated with impaired left ventricular diastolic filling in hypertensive subjects in this study. Since alterations in left ventricular filling have been identified as an early marker of hypertensive heart disease, the GNB3 C825T polymorphism may influence cardiac adaptation to increased afterload.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective and methodsTo determine whether hypertensive patients at risk for paroxysmal atrial fibrillation (AF) could be detected while in sinus rhythm, a computer-based 12-lead surface electrocardiogram was recorded in 50 hypertensive patients with history of paroxysmal AF (group A) and in 60 hypertensive patients without history of AF (group B). The maximum P-wave duration (Pmaximum), the minimum P-wave duration (Pminimum), P-wave dispersion (Pdispersion= Pmaximum− Pminimum), adjusted P-wave dispersion (APdispersion= Pdispersion/square root of the number of measurable leads), mean P-wave duration (mean P) and the standard deviation of the P-wave duration in all measured leads (SDP) were calculated.ResultsPdispersion, APdispersionand SDP were significantly higher in group A than in group B (Pdispersion, 52 ± 19 versus 41 ± 15 ms,P< 0.001; APdispersion, 15.2 ± 5.5 versus 11.9 ± 4.6 ms,P< 0.001; SDP, 16 ± 5 versus 13 ± 5 ms,P< 0.001). Pminimum, mean P and left ventricle ejection fraction (LVEF) were significantly lower in group A than in group B (Pminimum, 79 ± 18 versus 91 ± 13 ms,P< 0.001; mean P, 108 ± 18 versus 116 ± 13 ms,P= 0.005; LVEF, 64 ± 5 versus 69 ± 8%,P< 0.001). Pminimum, Pdispersion, mean P, SDP, APdispersionand LVEF were found to be significant univariate predictors of paroxysmal AF, whereas only Pminimum(P< 0.001) remained a significant independent predictor of paroxysmal AF in the multivariate analysis.ConclusionHypertensive patients at risk for paroxysmal AF could be detected while in sinus rhythm by computer-assisted electrocardiographic P-wave analysis.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias.ObjectiveTo estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres.MethodsCross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echo-cardiographic studies were performed in reference hospitals by trained observers (concordance Cohen κ index > 0.7) and analysed by a single observer.ResultsPrevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1–62.3] by Framingham criteria to 72.7% (95% CI 69.9–75.6) using the criteria of De Simoneet al.(J Am Coll Cardiol1995; 25: 1056–1062). Prevalence was higher in males by the Cornell–Penn criteria, but higher in females when using Framingham or De Simoneet al.criteria. Eccentric hypertrophy was more frequent (51.3–54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2–58.9%). Concentric remodelling was present in 6.5–11.4% and only 20.8–29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index.ConclusionPrevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Design and methodsLevels of dietary and serum potassium are thought to correlate inversely with vascular resistance and blood pressure. This study examined renal vascular resistance in perfused rat kidneys partially preconstricted with 10 μmol/l phenylephrine, quantifying changes in the resistance when levels of potassium in the perfusate ([K+]0) were varied between 2 and 80 mmol/l.ResultsIn kidneys from 17-week-old Wistar–Kyoto rats (WKY strain) fed a normal diet (American Institute of Nutrition AIN-76 diet), the resistance decreased when [K+]0was raised from 4 to 6–20 mmol/l, whereas resistance increased when [K+]0was either lowered to 2 mmol/l or raised above 25 mmol/l. The vasodilation that occurred at 13 mmol/l [K+]0was blocked by 100 μmol/l BaCl2and 10 μmol/l ouabain in an additive manner, suggesting that both the inward rectifier K+channel and the Na-K-ATPase underlie the dilation. Kidneys from spontaneously hypertensive rats (SHR strain) fed the AIN-76 diet displayed modestly enhanced vasodilations and vasoconstrictions as compared to WKY. A high-potassium diet (AIN-76 supplemented with 3.5% potassium citrate, provided for 8 weeks) led to exaggerated vasoconstrictive effects of [K+]0, and modestly enhanced vasodilations, in WKY rats. In contrast, the diet led to attenuated vasoconstrictions, and dramatically enhanced vasodilations, in the SHR strain. The diet did not affect the blood pressure increase or weight gain of either strain.ConclusionsChanges in the responsiveness of blood vessels to extracellular potassium might underlie some beneficial effects of high-potassium diets in hypertensive individuals.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the potential renal protective effects of a novel calcium channel blocker mibefradil in chronic renal failure.MethodWe compared the long-term effects of mibefradil with an angiotensin-converting enzyme inhibitor cilazapril on blood pressure, proteinuria, renal function and histological alterations inN-nitro-L-arginine methylester (L-NAME)-treated spontaneously hypertensive rats (SHR). Three groups of SHR were studied for 45 days: group 1 (n= 14), treated with L-NAME only (50 mg/l in the drinking water); group 2 (n= 15) L-NAME plus co-treatment with mibefradil (30 mg/kg per day); group 3 (n= 15), L-NAME plus co-treatment with cilazapril (10 mg/kg per day).ResultsBoth mibefradil and cilazapril attenuated the increased systolic blood pressure, and prevented the development of proteinuria and the decreased creatinine clearance (Ccr) seen at day 42 in the group treated with L-NAME alone. Notably, mibefradil had similar effects to cilazapril on proteinuria and Ccr, despite a reduced anti-hypertensive effect. All animals receiving mibefradil cotreatment remained alive throughout the experiment, whereas the mortality rate was 43% in SHR treated with L-NAME alone. Both mibefradil and cilazapril completely prevented renal structural damage as assessed by scoring glomerular, tubulo-interstitial and vascular lesions.ConclusionsOur data show that mibefradil prevented the development of hypertension and proteinuria, renal functional impairment and nephrosclerosis, and also improved animal survival. The renal protective effects of mibefradil were at least equivalent to those of an ACE inhibitor in this animal model of chronic renal failure.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 (insulin-dependent) diabetic patients with kidney disease.DesignThe study was a controlled, prospective, parallel, 10-year follow-up trial.Patients and interventionsA sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospectively followed for 10 years. Forty-five patients (intensified antihypertensive therapy; IT group) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians, consultants and local hospitals (routine antihypertensive therapy; RT group).Outcome measuresThe main endpoint was death; secondary endpoints were renal replacement therapy, blindness and amputation.ResultsBlood pressure was reduced in the IT group and increased in the RT group. During the follow-up period, 29 patients died, seven in the IT group and 22 in the RT group. The survival curves were significantly different (P= 0.0008). The main causes of death were cardiac. In a multiple Cox proportional hazards model, allocation to the IT group reduced the mortality risk [relative risk (RR) = 0.213; 95% confidence interval 0.089–0.509,P= 0.0005], while age (P= 0.0039) and mean blood pressure (P= 0.0113) increased this risk. In multiple Cox or multiple logistic regression models, the risks of dialysis (RR = 0.269, 95% confidence interval 0.110–0.656,P= 0.0039), blindness (odds ratio = 0.158, 95% confidence interval 0.037–0.684,P= 0.0136), and amputation (RR = 0.181, 95% confidence interval 0.047–0.703,P= 0.0135) were significantly lower in the IT group compared with the RT group (log rankP= 0.0008).ConclusionWe conclude that intensified antihypertensive treatment, based on a hypertension teaching and treatment programme, reduces long-term morbidity and mortality in patients with diabetic nephropathy.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID