摘要:

ObjectiveSubjects with multiple renal arteries have been shown to suffer more frequently from hypertension and to have higher blood pressures than subjects whose kidneys are supplied by single renal arteries. This study was carried out to determine whether subjects with multiple renal arteries also have higher renin activity.MethodsWe studied 62 consecutive patients who had undergone angiography for various reasons. They were divided into two groups. Group A comprised 29 patients whose kidneys were supplied by single arteries (male:female ratio 1.63, mean age 51.8 ± 1.9 years) while Group B comprised 33 patients with multiple renal arteries (male:female ratio 2, mean age 47.3 ± 2.3 years).ResultsBefore stimulation with frusemide, the plasma renin in Group A was 0.79 ± 0.13 ng angiotensin I/ml per h, while in Group B the corresponding figure was 1.73 ± 0.38 ng angiotensin I/ml per h. This difference was statistically significant (P= 0.0127). Thirty minutes later the plasma renin level in Group A was 2.43 ± 0.37 ng angiotensin I/ml per h versus a level of 3.86 ± 0.53 ng angiotensin I/ml per h in Group B (P=; 0.0169). Again, 30 minutes later the level was 2.59 ± 0.4 ng angiotensin I/ml per h in Group A, versus 3.7± 6 0.59 ng angiotensin I/ml per h in Group B (P=; 0.0495).ConclusionsWe conclude that patients with multiple renal arteries constitute a group who have high plasma renin activity and may therefore be prone to develop arterial hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveIn states of insulin resistance, the vasorelaxant actions of insulin are blunted, which may contribute towards the development of increased vascular tone/hypertension and reduced glucose uptake. To examine whether treating insulin resistance in hypertension restores the vascular actions of insulin, we studied the long-term effects of metformin on the contractile responses of isolated aortas from control and insulin-resistant, hyperinsulinaemic fructose-hypertensive rats in the presence and absence of insulin.Design and methodsSprague Dawley rats were divided into control, control metformin-treated, fructose and fructose metformin-treated groups (n= 8 per group). The treated groups received metformin (500 mg/kg per day for 6 weeks), following which isometric responses to noradrenaline (NA) and angiotensin II (A-II) were examined in thoracic aortas in the presence and absence of insulin (100 mU/ml for 2 h) using isolated organ-bath apparatus. In addition, endothelium-dependent and independent vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were also studied.ResultsMetformin treatment prevented the development of fructose-induced insulin resistance, hyperinsulinaemia and hypertension. Insulin attenuated the contractile responses to NA and A-II in control rat aortas; however, blood vessels from untreated fructose rats were refractory to insulin-induced vasodilation. Strikingly, long-term metformin treatment restored the vasodepressor actions of insulin in fructose rats. Metformin did not affect the contractile responses to NA or A-II in either control or fructose rats. In addition, metformin treatment restored ACh-induced endothelium-dependent vasorelaxation in aortas from fructose rats without affecting SNP-induced relaxation.ConclusionsThese data show, for the first time, that long-term metformin treatment corrects vascular insulin resistance and improves endothelium-dependent vasorelaxation in hypertension. These effects appear to be secondary to metformin-induced improvements in metabolic derangements (versus a direct vascular action of metformin). Improving the vascular effects of insulin may serve to decrease peripheral tone, attenuate blood pressure and improve insulin sensitivity.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo clarify the role of insulin resistance and hyperinsulinaemia in the pathogenesis of obesity-related hypertension.DesignAn open study comparing the effects of weight reduction by low-energy diet and treatment with troglitazone, an insulin-sensitizing agent.SettingA tertiary teaching hospital.PatientsThirty overweight hypertensive patients (15 men and 15 women, mean age 61 years, mean body mass index 29.1 kg/m2).InterventionsFifteen patients were assigned to a weight-reduction programme by low-energy diet (3360 kJ/day) for 3 weeks; the remaining 15 patients were treated with troglitazone (400 mg/day) for 8 weeks.Main outcome measuresCasual and ambulatory blood pressures, glucose and lipid metabolism, and insulin sensitivity.ResultsThe baseline values of body mass index, fasting and post-glucose plasma insulin, and casual and ambulatory blood pressures were comparable between the two groups. Weight reduction (4.1 ± 0.3 kg, mean ± SEM) was associated with significant decreases in plasma insulin, blood glucose, homeostasis model assessment (HOMA) insulin resistance index, serum triglyceride, casual blood pressure (7.7 ± 2.3/3.9 ± 1.4 mmHg) and 24 h blood pressure (8.3 6 1.9/ 4.3 ± 1.1 mmHg). Treatment with troglitazone caused comparable decreases in the metabolic parameters and HOMA index, but did not change casual or 24 h blood pressure (0.8 ± 3.4/0.8 ± 2.1 and 1.5 ± 2.4/1.0 ± 1.9 mmHg, respectively).ConclusionsInsulin resistance/hyperinsulinaemia may not have an important role in the pathogenesis of obesity-related hypertension. The antihypertensive effect of weight reduction seems to be mediated mainly by other mechanisms.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundAbnormalities in the vascular function of insulin are observed in insulin resistance, and hyperglycaemia is one of the important factors inducing insulin resistance.ObjectiveTo investigate the role of glucose in the interaction of insulin and β-adrenergic signalling systems in vascular smooth muscle cells (VSMC).MethodsAfter cells were treated with D-glucose (5– 25 mmol/l) and insulin (100 nmol/l), adenylyl cyclase activity was measured in the presence of isoproterenol, forskolin, and cholera toxin. Assays for insulin-induced activities of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) were performed.ResultsIn the presence of low glucose concentrations (5 mmol/l), insulin enhanced isoproterenol-, forskolin-and cholera toxin-stimulated adenylyl cyclase activities. This stimulatory effect was abolished by PI3-K inhibitors, wortmannin, or LY294002. In contrast, in the presence of high glucose concentrations (25 mmol/l), insulin attenuated isoproterenol-stimulated activity but not cholera toxin-or forskolin-stimulated activity. Insulin-stimulated activities of IRS-1 and PI3-K, but not MAPK activity, were also attenuated in the presence of high concentrations of glucose. The MAPK kinase inhibitor, PD98059, abolished the inhibitory effect of insulin on the β-adrenergic signalling system. Troglitazone and pioglitazone prevented this inhibitory effect of insulin by restoring IRS-1 and PI3-K activities.ConclusionsIn the presence of low glucose concentrations, insulin stimulates the β-adrenergic signalling system through the IRS-1/PI3-K pathway. However, in the presence of high glucose concentrations, the effect of insulin is switched to an inhibitory one, through the MAPK pathway. Our finding suggests that high glucose concentrations modify the cross-talk between insulin and the β-adrenergic signalling systems in VSMC.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH).DesignThe LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence.SettingEuropean hospitals, general practitioners and cardiologists.PatientsHypertensive patients aged ≥ 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients.InterventionsIndapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks.Main outcome measuresLVMI variation in the per-protocol population.ResultsIndapamide SR 1.5 mg significantly reduced LVMI (−8.4 ± 30.5 g/m2from baseline;P< 0.001), but enalapril 20 mg did not (−1.9 ± 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: −6.5 g/m2,P= 0.013 (−4.3 g/m2when adjusted for baseline values;P= 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months.ConclusionsIndapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo assess the ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity (Doppler E/A ratio) before and after adjustment for age in patients with moderate to severe hypertension, in whom left ventricular diastolic dysfunction is an early finding. Mitral flow patterns can be used to assess diastolic filling characteristics, and the Doppler E/A ratio is the parameter most commonly used, although it is known to be strongly age dependent. There are no established normal values for this ratio.DesignRetrospective data analysis.SettingA 2000-bed tertiary-care teaching hospital.PatientsWe studied 190 patients (99 women and 91 men; ages 55 ± 13 years) with moderate to severe hypertension.InterventionsThe ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity was measured. As this ratio depends on age, aZscore was calculated to control for this influence. TheZscore is the standardized normal deviation of the mean, with a normal value of 0 ± 2.Main outcome measuresSensitivities and specificities for detecting an age-dependent reduction in Doppler E/A score (Zscore less than −2) with a non-age-dependent Doppler E/A ratio (less than 1) were calculated.ResultsIn 106 of the patients (56%) the Doppler E/A ratio was less than 1.0. Only nine patients (4.7%) had aZscore less than −2. The sensitivity of the Doppler E/A ratio threshold of 1.0 for detecting aZscore less than −2 was 0.89 and the specificity was 0.46. AZscore less than −2 was found only in patients younger than 45 years.ConclusionsThe Doppler E/A ratio was reduced in a large proportion of our patients. However, after correction for age it was decreased in only 4.7% of these patients. The use of a single Doppler E/A ratio threshold value has a weak diagnostic power to detect age-independent changes in mitral flow patterns.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundThe main determinants of diastolic function—pre-and afterload of the heart—are affected by the haematocrit, but the relation between haematocrit and diastolic function is unclear.ObjectiveTo study the association between interindividual haematocrit values and diastolic function, by echocardiography.DesignIn a cross-sectional survey, blood pressure, haematocrit values, and high-quality Doppler indexes of left ventricular filling were obtained in 1297 individuals, 25–74 years of age, and analysed by regression analyses.ResultsHaematocrit and systolic blood pressure were strongly correlated (r= 0.23;P< 0.0001). Moreover, haematocrit was inversely correlated with the peak velocity of early left ventricular filling and with the peak velocity of early filling divided by late filling (E/A ratio; bothP< 0.005). Left ventricular isovolumic relaxation time (IVRT) was positively associated with haematocrit (r= 0.18,P< 0.001). In individuals with an abnormal Doppler filling pattern (E/A<50 years< 1, E/A> 50years< 0.5, or IVRT< 30years> 92 ms, IVRT30–50years> 100 ms or IVRT>50 years> 105 ms;n= 119), greater haematocrit values were observed than in those with normal diastolic parameters (P< 0.001). Conversely, individuals with an increased haematocrit (> 50% in men, > 45% in women;n= 16) had a greater risk of presenting with abnormal left ventricular filling (31.3%) compared with individuals with normal (12.1%;n= 898;) or low (< 40% in men, < 35% in women: 10.5%,n= 38;P= 0.07) haematocrit. Strong and significant associations between haematocrit and Doppler indexes of left ventricular filling were confirmed after adjustment for multiple potential confounders including blood pressure, antihypertensive medication and body mass index. Similarly, blood pressure and parameters of diastolic filling were strongly associated correlations that were not affected by inclusion of haematocrit values into the regression model.ConclusionThe data point to substantial adaptations of diastolic filling in response to both blood pressure and the characteristics of the medium that is propelled by the heart. Therefore, in addition to blood pressure values, the variability of haematocrit values should be considered when diastolic function is being evaluated by Doppler echocardiography.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe purpose of this study was to determine the relative importance of bradykinin and nitric oxide (NO) in mediating renal responses to altered sodium intake in Dahl salt-resistant (Dahl-SR) and salt-sensitive (Dahl-SS) rats.Design and methodsDahl-SR and Dahl-SS rats consumed a diet containing 0.15% (low) or 4.0% (high) sodium chloride for 10 days. A microdialysis technique was then used to measure renal cortical interstitial fluid (RIF) cyclic 39,59-guanosine monophosphate (cGMP) production in anesthetized rats, under baseline conditions and during acute cortical infusion of either the bradykinin B2 receptor antagonist icatibant or the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME). Urine sodium excretion was monitored simultaneously by ureter cannulation.ResultsBaseline sodium excretion was similar in the two types of rats, but RIF cGMP was significantly elevated in Dahl-SR compared to Dahl-SS rats on both low and high sodium diets. Icatibant infusion significantly reduced both RIF cGMP and sodium excretion in Dahl-SR rats during low sodium intake, but had no effect in Dahl-SS rats on either diet. L-NAME infusion significantly reduced sodium excretion in Dahl-SR and Dahl-SS rats, during both low and high sodium intake. L-NAME infusion caused a significant reduction in RIF cGMP in Dahl-SR and Dahl-SS rats on low sodium diet, but reduced RIF cGMP only in Dahl-SR rats on high sodium diet.ConclusionThese data suggest a potential role for cortical bradykinin, but not NO, in mediating the differences in the renal response to low sodium intake between Dahl-SR and Dahl-SS rats.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveAlterations in renal nitric oxide (NO) are involved in the hypertension of the Dahl salt-sensitive (Dahl-SS) rat. We sought to identify the kinetics and sites of expression of the major NO synthase (NOS) isoforms.DesignThe renal expression of the major NOS were examined in Dahl-SS and salt-resistant rats (Dahl-SR) while on a low salt (0.1% NaCl) diet at 3 and 9 weeks of age.MethodsRenal biopsies from Dahl-SS and Dahl-SR rats were compared for evidence of renal injury and for alterations in expression of the NOS enzymes by quantitative immunohistochemistry.ResultsAt 3 weeks of age Dahl-SS and Dahl-SR rats have normal renal histology and similar immunohistochemical expression of NOS1, −2, and −3. At 9 weeks Dahl-SS rats had significantly higher blood pressure than Dahl-SR rats (P< 0.005), and lower macula densa NOS1 (P< 0.05) and cortical and medullary NOS3 (P< 0.05). NOS2 was reduced in cortical tubules in biopsies showing severe tubulointerstitial damage, but was not significantly different between Dahl-SS and Dahl-SR groups as a whole. Dahl-SS rats also manifested glomerular and tubulointerstitial injury. Tubular expression of osteopontin (OPN), which is an inhibitor of NOS2, correlated with the systolic BP in individual Dahl-SS rats (r2= 0.80,P< 0.0001).ConclusionTubulointerstitial injury and the loss of NOS occur after birth and parallel the development of hypertension. We suggest that the structural and functional changes that occur with renal injury in the Dahl-SS rat may contribute to the development of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the role of an activated endothelin system in the renal dysfunction observed in chronic heart failure after myocardial infarction.MethodsIn rats with heart failure after myocardial infarction and in sham-operated animals (Sham), we investigated the effect on renal function of long-term oral treatment with the selective endothelin A (ETA) receptor antagonist, LU 135252 (30 mg/kg per day; groups MI/LU and Sham/LU) or placebo (groups MI/P, Sham/P). Only animals with extensive myocardial infarction (at least 46% of the left ventricle) were included in the study. Infarct size was matched between groups MI/P and MI/LU. Endogenous creatinine clearance, fractional sodium excretion, and plasma and urinary concentrations of endothelin were determined 12 weeks after myocardial infarction.ResultsEndogenous creatinine clearance was significantly lower in group MI/P than in group Sham/P (MI/P:0.64 ± 0.05, Sham/P: 0.81 ± 0.04 ml/min per 100 g body weight;P= 0.01 (means 6 SEM)). Treatment with LU 135252 completely prevented the decline in creatinine clearance in rats with chronic myocardial infarction (MI/LU: 0.98 ± 0.21; Sham/LU: 0.83 ± 0.10). Fractional sodium and protein excretion did not differ among the four groups. Group MI/P had a marked increase in plasma endothelin concentrations, which was not affected by treatment with LU 135252. Urinary endothelin excretion was significantly lower in group MI/P than in group Sham/P. In the treatment groups, no difference could be observed between animals that had suffered myocardial infarction and the sham-operated group, although LU 135252 markedly increased the urinary excretion of endothelin.ConclusionOur data demonstrate a restoration of impaired renal function in chronic ischaemic heart failure by treatment with the selective ETA receptor antagonist, LU 135252. These results offer a promising therapeutic option for the treatment of renal insufficiency in patients with chronic heart failure.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID