摘要:

Ambulatory blood pressure monitoring (ABPM) has now become an established clinical tool. It is appropriate to take stock and assess the situation of this technique.Update on equipmentImportant improvements in equipment have occurred, with reductions in weight, in awkwardness and in noisiness of the machines, better acceptability and tolerance by the patients, and better reliability. Validation programmes have been proposed and should be referred to. Limitations of the technique persist with intermittent recording in current practice. The reproducibility is limited in the short-term while recording over 24 h is acceptable.Diagnosis and prognosisWhite-coat effect (WCE) is manifested as a transient elevation in blood pressure during the medical visit. The frequency of this phenomenon, the size of the effect, age, sex and level of blood pressure (BP) or the situation of occurrence (general practitioner, specialist or nurse) have been interpreted differently. It does not seem that WCE predicts cardiovascular morbidity or mortality. White-coat hypertension (WCH) is diagnosed on the evidence of abnormal clinical measures of BP and normal ABPM. The latest upper limits of normality by ABPM recommended by the JNCVI are < 135/85 mmHg while patients are awake and < 120/75 mmHg while patients are asleep. If we accept these upper limits of normality in ABPM, WCH does not appear to be a real problem as regards risk factors or end-organ effects. In terms of prognosis, data are limited. Cardiovascular morbidity seems low in WCH but identical to that of hypertensive subjects in these studies. However, further studies are needed to confirm these results. WCH does not appear to benefit from anti-hypertensive treatment. It is obvious that the lower the BP regarded as the limit of normality, the less likely the occurrence of secondary effects of metabolism, or end-organ effects or complications in those classified as hypertensive.24 hour cycleOne of the most specific characteristics of ABPM is the possibility of being able to discover modification or alteration of the 24 h cycle of BP. Non-dippers are classically defined as those who show a reduction in BP of less than 10/5 mmHg or 10% between the day (06.00–22.00 h) and the night, or an elevation in BP. In contrast, extreme dippers are those in whom the BP reduction is greater than 20%.Cardiovascular systemThe data remain inconclusive with regard to the existence of a consistent relationship between the lack of a nocturnal dip in blood pressure and target organ damage. As regards prognosis, it seems that an inversion of the day–night cycle is of pejorative significance.Cerebrovascular systemAlmost all studies have shown that non-dippers had a significantly higher frequency of stroke than dippers. In contrast, too great a fall in nocturnal BP may be responsible for more marked cerebral ischaemia.Renal systemNon-dippers have a significantly elevated median urinary excretion of albumin. There is a significant correlation between the systolic BP and nocturnal diastolic BP, and urinary excretion of albumin. Various studies have confirmed the increased frequency of change in the 24 h cycle in hypertensive subjects at the stage of renal failure.DiabetesBP abnormalities should be considered as markers of an elevated risk in diabetic subjects but cannot be considered at present as predictive of the appearance of micro-albuminuria or other abnormalities. ABPM is thus of interest in type I or type II diabetes both in the initial assessment and in the follow-up and adaptation of treatment.Pharmaco-therapeutic usesThe introduction of ABPM has truly changed the means and possibilities of approach to the study of the effects of anti-hypertensive medications, with new possibilities of analysis such as trough–peak ratio smoothness index, etc.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the impact of self-monitoring of blood pressure values (BPS) as compared with office blood pressure measurements (BPO) on the progression of diabetic nephropathy.DesignLong-term, follow-up cohort study.Subjects and methodsHypertensive, type 1 diabetic patients with overt diabetic nephropathy were investigated. Patients initially participated in a hypertension treatment and teaching programme including extensive advice on blood pressure self-monitoring. Self-monitoring and office blood pressure values were continuously assessed during the entire follow-up period. Progression of diabetic nephropathy over the study period was individually assessed as the mean decline of glomerular filtration rate (GFR) per patient per year. Baseline and follow-up parameters were included in stepwise multiple regression analyses with the decline of GFR per year as the dependent variable.ResultsSeventy-seven type 1 diabetic patients (37 women, 40 men) were followed for a mean period of 6.2 ± 2.8 years (mean ± SD; range 2–12) resulting in a total of 481 patient-years. During the follow-up period, mean BPO decreased from 166/95 at baseline to 154/89 mmHg during follow-up, and mean BPSfell from 159/93 to 138/83 mmHg. The mean decline of GFR was 4.1 ± 5.6 ml/min per year. Loss of kidney function was significantly correlated with proteinuria, blood pressure and glycosylated haemoglobin values. In the multiple regression analyses, BPSpredicted the loss of renal function better than BPO(R2= 0.52 versus 0.42). The simple correlation between BPSand GFR decline was higher compared to BPOand GFR (r= −0.42; P < −0.0001 versus −0.33; P < 0.004).ConclusionBlood pressure self-monitoring values are a better predictor of progression of diabetic nephropathy when compared with office blood pressure measurements.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesObstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses.Design and methodsFull overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (ΔBP) from pre- to post-apnoea termination was measured for each apnoeic cycle.ResultsOnly 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (ΔMAP) 12 ± 3 mmHg during the follicular phase and 20 ± 3 mmHg during the luteal phase,P< 0.001; REM ΔMAP 11 ± 3 mmHg during the follicular phase and 23 ± 3 mmHg during the luteal phase,P< 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in nonovulating subjects.ConclusionsObstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesWe have previously shown that in the rat a diet high in cholesterol and deficient in vitamin E and selenium results in hypercholesterolaemia and increased lipid oxidation. We utilized this model to determine whether rats given this diet develop impaired endothelium-dependent relaxation mediated by nitric oxide (NO) in mesenteric and in renal vessels. In addition, we tested whether the impairment is due to (i) decreased endothelial NO synthase activity, (ii) increased NO inactivation and/or (iii) increased production of the endothelium-derived constricting factors thromboxane A2/prostaglandin H2and endothelin-1. We also investigated whether endothelial dysfunction induced by dyslipidaemia increases the sensitivity for the development of hypertension in response to high dietary salt.MethodsMale Dahl salt-sensitive (DSS) rats were divided into three groups and received a standard diet (control group), a high (4%) cholesterol diet (HChol), or a high cholesterol diet deficient in the anti-oxidants vitamin E and selenium (HChol-Def). The NaCl content of these diets was 0.5%. After 18 weeks we studied endothelium-dependent relaxation in response to acetylcholine (ACh) in aortas and in isolated perfused preparations of mesenteric arteries and kidneys. In some experiments, ifetroban, a thromboxane A2/prostaglandin H2receptor antagonist, was added to the organ bath or the perfusion buffer. Vascular responses to endothelin-1 as well as to BQ-123, an endothelin A receptor blocker, were studied in the isolated perfused kidneys. In addition, two extra groups of rats were fed a diet high in sodium chloride (2%): one of the groups received the normal cholesterol diet whereas the other group received the diet high in cholesterol and deficient in vitamin E and selenium.ResultsCompared to normocholesterolemic rats, responses to ACh were significantly impaired in aortas, mesenteric arteries and kidneys of HChol-Def rats (P < 0.0l). Endothelial NO synthase activity (conversion of [14C]L-arginine to [14C]L-citrulline) was similar in aortas of control, HChol and HChol-Def rats; thus suggesting that impaired endothelium-dependent relaxation in the HChol-Def rats was not due to decreased cNOS catalytic activity. Ifetroban improved the impaired endothelium-dependent relaxation in mesenteric vessels, but not in aortas and kidneys. Endothelin-1 (ET-1: 10−13−10−11mol/l) elicited NO-mediated relaxations in kidneys of control rats but not in kidneys of HChol-Def; blockade of ET-1 with BQ-123, an ETA receptor blocker, did not improve NO-mediated relaxation of HChol-Def. Despite impaired endothelium-dependent relaxation in renal and mesenteric vessels, HChol-Def DSS rats failed to develop hypertension (systolic blood pressure 144 ± 1 in control and 150 ± 2 mmHg in HChol-Def) but manifested a significant increase in sensitivity to the pressor effects of a high (2% NaCl) dietary salt content during the initial 10 weeks of the study, although the final blood pressure at 18 weeks was similar in both groups.ConclusionThese studies support the notion that (i) products of lipid oxidation may reduce NO bioactivity without affecting endothelial NO synthase mass or catalytic activity, (ii) the mechanisms involved in the endothelial dysfunction induced by hypercholesterolaemia and oxidized lipids may differ among vascular beds, and (iii) decreased NO bioavailability does not necessarily result in systemic hypertension, but it may enhance the sensitivity to the hypertensinogenic effect of dietary salt.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate the mechanisms of vascular uptake of prorenin and renin and to explore the possibility of vascular activation of prorenin.Design and methodsHuman umbilical vein endothelial cells (HUVECs) cultured in a chemically defined medium were incubated with recombinant human prorenin or renin in the presence or absence of putative inhibitors of renin internalization. Cell surface-bound and internalized prorenin or renin were separated by the acid-wash method and were quantified by enzyme-kinetic assays. The activation of prorenin was also monitored by a direct immunoradiometric assay (IRMA) with use of a monoclonal antibody directed against the -p24-Arg to −1 p-Arg C-terminal propeptide sequence of prorenin.ResultsProrenin and renin were internalized at 37°C in a dose-dependent manner; with 1000 μU prorenin/ml medium, the quantity of cell-associated prorenin after 3 h of incubation was 9.3 ± 1.0 μU/4 × 105cells, and with 75 000 μU/ml medium it was 670 ± 75 μU/4 × 105cells (mean ± SD;n= 5). Results for renin were similar. Prorenin that had been treated with endoglycosidase H to remove N-linked oligosaccharides was not internalized. Addition of mannose 6-phosphate (M-6-P) to the medium caused a dose-dependent inhibition of renin and prorenin internalization. Fifty per cent inhibition was observed at 70 μmol/M-6-P, whereas mannose 1-phosphate, glucose 6-phosphate and α-methylmannoside at this concentration had no effect Ammonium chloride (50 mmol/l) and monensin (10 μmol/l) also inhibited internalization. Prorenin was activated by HUVECs, and cell-activated prorenin was only found in the internalized fraction, whereas the surface-bound prorenin remained inactive. Thus, it appears that the activation of prorenin took place at the time of its internalization or thereafter. The results of the prorenin IRMA indicated that activation was associated with proteolytic cleavage of the propeptide.ConclusionsOur findings provide evidence for M-6-P receptor-dependent endocytosis of (pro)renin and proteolytic prorenin activation by vascular endothelial cells.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate whether differences exist in the mechanical properties of large arteries between white and black subjects.DesignEighty-two white (49 normotensive and 33 untreated hypertensive) and 38 black (24 normotensive and 14 untreated hypertensive) adult male volunteers were studied in a cross-sectional study.MethodsCarotid-femoral pulse wave velocity was measured as an index of arterial stiffness, using a recently developed non-invasive automatic device, and compared between white and black subjects before and after the adjustment for age. The slope of regressions for pulse wave velocity and systolic blood pressure were also compared between racial groups.ResultsIn the normotensive group, white subjects presented higher mean values of pulse wave velocity than blacks while the opposite behavior was found in the hypertensive group. After adjustment for age, significant differences in pulse wave velocity between whites and blacks became evident in the normotensive (whites 8.15 ± 0.04 versus blacks 7.75 ± 0.02 m/s;P< 0.001) and hypertensive (whites 8.88 ± 0.02 versus blacks 9.30 ± 0.17 m/s;P< 0.001) groups. Linear regression analysis for age-adjusted pulse wave velocity and systolic blood pressure showed that the slope was significantly greater in blacks than in whites (0.040 ± 0.002 versus 0.019 ± 0.001 m/s;P< 0.001).ConclusionThese data indicate that there is a greater pressure-dependent increase in aortic stiffness in blacks than in whites. This finding points towards major differences in mechanical properties of large arteries between these racial groups.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe γ subunit of the epithelial Na channel (γENaC) has been implicated in Liddle's syndrome. The objective of this study was to examine its status in essential hypertension.Design and methodsThe search for molecular variants was performed using the SSCP technique after determination of the intron–exon boundaries of the transcribed sequence. We found an additional 205 bp intron splitting the published exon 10 in two. The last exon of γENaC was tested with samples from a series of 245 normotensive patients and 453 hypertensive subjects (383 Caucasians, 70 Afro-Caribbeans), all probands of hypertensive families in the HYPERGENE data set. The search was extended to the other 11 transcribed exons in a subset of 65 patients with low-renin profile.ResultsFour neutral polymorphisms were detected, three in the third exon of the gene (T387C, T474C, C549T) and one in the last exon (C1990G). These four variants were found with similar frequencies in hypertensive and normotensive Caucasian subjects as well as in patients with low-renin profile. Hypertensive Caucasians and hypertensive subjects of African ancestry also had similar frequencies. Lastly, we found two rare mutations, one the insertion of a proline residue at position 594 of the mature protein (594insP), the other an Arg-to-His substitution at position 631 (R631H). Compared to wild-type (1.00 ± 0.42,n= 26), expression of the 594insP (1.10 ± 0.43,n= 26) and R631H (0.97 ± 0.43,n= 26) variants inXenopusoocytes produced no significant increase in Na+current.ConclusionsScreening of the entire coding sequence of γENaC does not suggest that this subunit is frequently involved in essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveWe investigated the determinants of plasma renin activity (PRA) and plasma levels of angiotensin-coverting enzyme (pACE), including the effect of the D/I polymorphism of the angiotensin-converting enzyme (ACE) gene, in monozygotic (MZ) and dizygotic (DZ) twins.MethodsSixty-nine pairs of twins underwent measurements of blood pressure, pACE and ACE D/I genotyping. In addition, in 30 pairs ambulatory blood pressure (ABP) monitoring was carried out. To ascertain twin's zygosity, some highly discriminating variable number of tandem repeats micro- and mini-satellite systems were analysed by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis and silver staining. The D/I polymorphism was assessed by PCR; pACE was measured in triplicate with a colorimetric assay, and PRA by a commercial kit. In DZ twins, identity by descent of the D/I alleles was examined by PCR amplification of a highly polymorphic simple sequence repeat at the human growth hormone gene.ResultspACE levels were significantly (P< 0.01) higher in DD (9.27 ± 2.60 IU/I, mean ± SD) than in II (6.68 ± 3.0), with DI having intermediate levels (7.93 ± 2.7). No difference of PRA between different D/I genotypes was found. Twin data analysis showed a statistically significant heritability of pACE, but not of PRA. No differences between MZ and DZ twins in PRA, pACE and the relationship of the D/I genotype with pACE was found. Besides showing that the D/I genotype was the most important predictor of pACE, a multivariate analysis demonstrated that identity by descent of the D/I allele, as assessed by growth hormone (GH) genotyping, also significantly affected pACE.ConclusionsIn this study of normotensive twins, pACE and not PRA showed significant heritability, the former being tightly associated with the D/l ACE gene polymorphism, and/or with a quantitative trait locus in linkage disequilibrium with it.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe presence of the deletion allele of the angiotensin-converting enzyme (ACE) I/D polymorphism is associated with an excess risk of vascular disease and diabetic nephropathy.ObjectiveTo examine the importance of this polymorphism as a determinant of hypertension and impaired glucose metabolism in a population-based study of three ethnic groups and assess the potential modifying effect of gender.DesignPopulation-based cross-sectional study in South London. The population-based sample of 1577 men and women, age 40–59 years, was obtained from stratified random sampling of general practice lists where 25% of the residents were born outside the UK. The ACE I/D polymorphism was determined for 1366 individuals (86.6%): 462 whites, 462 of African descent and 442 of South Asian origin.ResultsThe genotype frequency within each ethnic group was in Hardy–Weinberg equilibrium. The frequencies were similar in whites and those of African descent (II, ID, DD: 18.4%, 49.6%, 32.0% for whites and 18.4%, 50.5%, 30.9% for those of African descent), but there was a much higher frequency of the II genotype in those of South Asian origin (39.8%, 41.8%, 18.3%; χ2= 77.6;P< 0.0001). There was no association between the I/D polymorphism and impaired glucose metabolism in any ethnic group. There were also no significant associations between the I/D polymorphism and hypertension in whites and in those of South Asian origin. This contrasts with a highly significant association between the D allele and hypertension in women of African descent (OR = 2.54; 95% CI 1.38–4.65;P= 0.003) but not in men of African descent (0.79; 0.36–1.72) (test for differences between sexesP= 0.023).ConclusionsThese observations provide estimates of the frequency distribution of the ACE I/D polymorphism in whites, in people of African descent and in people of South Asian origin. Moreover, these results highlight the potential importance of gender-dependent interactions between genetic background and expression of hypertensive phenotype.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveDevelopment of internally quenched fluorogenic substrates for sensitive and continuous assays of angiotensin I-converting enzyme (ACE).DesignWe synthesized internally quenched fluorogenic bradykinin-related peptides introducing Abz (ortho-aminobenzoic acid) and EDDnp (N-[2,4-dinrtrophenyl]-ethylenediamine) at their N- and C-terminal groups, respectively, and these were assayed as ACE substrates. We examined two series of peptides, Abz-GFSPFRXEDDnp and Abz-GFSPFXQ-EDDnp (X, various amino acids).MethodsHydrolysis of the fluorogenic substrates by ACE was followed by continuous recording of the rising fluorescence (λem= 420 nm and λex= 320 nm). The peptides were obtained by solid-phase synthesis or by classical solution methods.ResultsDespite of the blocked C-terminal sequences, the internally quenched bradykinin-related peptides were hydrolysed by ACE. The best substrates for plasma guinea pig ACE were Abz-GFSPFRA-EDDnp and Abz-GFSPFFQEDDnp, in which the fluorescence appeared after the first cleavage that occurred at R-A and F-Q bond, respectively. This ACE activity was sensitive to NaCl concentration and the optimum pH is greater than 8.0. Measurements of ACE activity with Hip-His-Leu and Abz-QFSPFFQ-EDDnp in the serum of 20 healthy patients correlated closelyr= 0.959). Complete inhibition of the hydrolysis of Abz-GFSPFFQ-EDDnp by human serum was observed with captopril and lisinopril.ConclusionsWe describe internally quenched fluorogenic substrates for ACE devoid of free C-terminal carboxyl group. They are convenient tools for ACE studies as they permit continuous fluorimetric measurements of the enzymatic activity, even in human serum.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID