Showing papers in "Journal of Hypertension in 1999"

Effects of obstructive sleep apnea on endothelin-1 and blood pressure.

Abstract: ObjectiveTo evaluate blood pressure and humoral vasoconstrictor responses to recurrent episodes of obstructive sleep apnea and the effects of therapy by means of continuous positive airway pressure.Patients and methodsWe prospectively evaluated overnight changes in hemodynamics, oxygen saturation, t

How to assess sympathetic activity in humans.

Abstract: Sympathetic factors play a central role not only in cardiovascular homeostatic control but also in the pathogenesis and/or in the progression of several cardiovascular diseases, such as essential hypertension, myocardial infarction, cardiac arrhythmias and congestive heart failure. This explains why assessment of adrenergic neural function in humans has been, and certainly still remains, one of the major fields in cardiovascular research. The present paper will review in detail the haemodynamic, pharmacological, biochemical, neurophysiological, neurochemical and neural imaging techniques by which sympathetic activity is assessed in humans, highlighting the main advantages and limitations of each of them. Although plasma noradrenaline measurement represents a useful guide to assess sympathetic neural function, direct recording of sympathetic nerve traffic via microneurography and noradrenaline radiotracer methods have in recent years largely supplanted the plasma noradrenaline approach. This is because they allow (1) discrimination between the central or peripheral nature of increased plasma noradrenaline levels, and (2) precise estimation of the behaviour of regional sympathetic neural function both under physiological and pathological conditions. In contrast, the approach based on spectral analysis of heart rate and blood pressure signals has been shown to have important limitations which prevent the method from faithfully reflecting sympathetic cardiovascular drive. Neural imaging techniques, which require expensive technical support, allow direct visualization of sympathetic enervation of human organs, thus providing information on the 'in vivo' metabolism of noradrenaline in different cardiovascular districts. Although technical improvements have allowed a more precise assessment of human adrenergic function, no technique so far available can be viewed as a 'gold standard' with which the others might be compared. Limitations and disadvantages of the various techniques may be reduced if these methods are seen as being complementary and employed in combination, allowing more reliable information to be achieved on the sympathetic abnormalities characterizing cardiovascular diseases, and thus hopefully providing a stronger rationale for newer therapeutic approaches involving pharmacological modification of the sympathetic nervous system and adrenoreceptors.

Neural mechanisms in human obesity-related hypertension.

Abstract: ObjectiveTwo hypotheses concerning mechanisms of weight gain and of blood pressure elevation in obesity were tested. The first hypothesis is that in human obesity sympathetic nervous system underactivity is present, as a metabolic basis for the obesity. The second hypothesis, attributable to Landsbe

Pulse pressure as a risk factor for cardiovascular events in the MRC Mild Hypertension Trial.

Abstract: Objectives The aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension, and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients. Methods Logistic regression and Cox regression analyses were used to compare systolic and diastolic blood pressure, pulse pressure and mean blood pressure as predictors of coronary events and stroke in the MRC Mild Hypertension Trial. The effects of anti-hypertensive drug treatment with bendrofluazide and propranolol on pulse pressure were assessed using 1-year follow-up data. Event rates in the placebo-treated group and responses to anti-hypertensive treatment were measured in quartiles of age-adjusted entry pulse pressure. A ‘four-corners’ analysis was performed, with subjects divided into the upper and lower halves of the distributions of systolic and diastolic blood pressure at entry. Results Pulse pressure was a stronger predictor of coronary events than systolic, diastolic or mean blood pressure in males by logistic regression. Pulse pressure was similar to systolic pressure as a coronary event predictor on Cox regression. Stroke was predicted most strongly by mean blood pressure. Fatal and non-fatal coronary event rates increased progressively in ascending quartiles of age-adjusted pulse pressure, but there was also a strong correlation with systolic blood pressure. The values of partial logistic regression coefficients in models containing both systolic and diastolic blood pressure also supported a role for pulse pressure in predicting coronary events and for mean blood pressure in predicting stroke. Coronary risk, but not stroke, was inversely related to diastolic blood pressure in the four-corners analysis. In a Cox model, regressions of coronary event probability on systolic blood pressure at entry were significantly and inversely related to diastolic blood pressure categorized in quartiles. Bendrofluazide but not propranolol decreased pulse pressure significantly and was associated with a reduction in cardiovascular events overall, but no definite relationship between the effect of drugs on pulse pressure and specific responses to treatment was seen. Conclusion Pulse pressure is a strong risk factor for coronary events in untreated hypertensive male subjects in the MRC Mild Hypertension Trial, whereas stroke is best predicted by mean blood pressure. Bendrofluazide and propranolol have different effects on pulse pressure which may be related to their relative efficacy in the treatment of hypertension, but this possibility requires further study in more suitable populations.

Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice.

Abstract: Objective Recent advances in understanding the neuroendocrine pathways regulating appetite, metabolism and body weight afford an opportunity to explore further the mechanisms by which obesity influences arterial pressure, ob/ob(Lep ob /Lep ob ) mice have a mutation in the ob gene and are leptin-deficient. Leptin possesses pressor actions and has been shown to increase arterial pressure when infused chronically or over-expressed transgenically. In contrast, agouti yellow obese(A y ) mice have over-expression of an agouti peptide that blocks melanocortin receptors. Stimulation of melanocortin receptors by α-melanocyte-stimulating hormone decreases arterial pressure. Design and methods This study measured arterial pressure in leptin-deficient ob/ob mice, agouti yellow obese mice and their lean controls to test the hypothesis that the effects of obesity on arterial pressure are importantly influenced by the genetic and neuroendocrine mechanisms causing the obesity. We measured arterial pressure directly in conscious ob/ob mice (n = 14), agouti yellow obese mice (n = 6) and the same number of lean littermates. Results Body weight was nearly twice as high in ob/ob mice as in their lean controls, but mean arterial pressure was significantly lower in ob/ob mice (92 ± 3 mmHg) compared with their lean controls (106 ± 2 mmHg; P=0.00017). In contrast, mean arterial pressure was significantly higher in agouti yellow obese mice (124 ± 3 mmHg) than in their lean controls (99 ± 1 mmHg; P = 0.000002) despite the fact that the agouti mice had milder obesity. Conclusions This study prompts three conclusions: (1) leptin-deficient ob/ob mice and agouti yellow obese mice have contrasting blood pressure responses to obesity, (2) obesity does not invariably increase arterial pressure in mice, and (3) the arterial pressure response to obesity may depend critically on the underlying genetic and neuroendocrine mechanisms.

The Hypertension Optimal Treatment study and the importance of lowering blood pressure.

Abstract: ObjectiveIn this meta-analysis, we attempted to derive pooled estimates for the putative associations between various cardiovascular–renal disorders and the M235T polymorphism of the angiotensinogen gene.MethodsCase–control studies were combined, using the Mantel and Haenszel approach. Joint P value

Co-expression of renin-angiotensin system genes in human adipose tissue.

Abstract: Objective The renin-angiotensin system plays a central role in blood pressure regulation, both by affecting renal function and by modulating vascular tone and structure. Recent studies in rodents demonstrated the existence of several components of this system in adipose tissue. The activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in obesity-associated hypertension. Few data are available on the presence of renin-angiotensin system components in human adipose tissue. Materials and methods In order to explore the expression of renin-angiotensin system genes in human adipose tissue and adipocytes, total RNA was isolated from whole adipose tissue (subcutaneous and omental) or cultured adipocytes (mammary) and subjected to reversetranscriptase polymerase chain reaction with primers specific for human angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors. Results Angiotensinogen, angiotensin converting enzyme and type 1 angiotensin receptor genes were widely expressed, both in human adipose tissue and in cultured human adipocytes. Furthermore, we found expression of the chymase and renin-binding protein genes in these samples. Conclusions Our findings suggest the presence of a local renin-angiotensin system in human adipose tissue, with adipocytes being an important part of this system, and prompt speculation that this local renin-angiotensin system may be involved in obesity-related disorders, including hypertension and the metabolic syndrome.

How to assess glomerular function and damage in humans.

Abstract: In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations. Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass. Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration-time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration-time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently, 125l-iothalamate, 99mTc-diethylenethiaminepenta-acetic acid and 51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR. In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance. Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages.

Abstract: Background We have demonstrated that accumulated macrophages in human coronary arteries strongly express angiotensin converting enzyme in accordance with the development of atheromatous plaques. However, there are few reports on the regulation of the renin-angiotensin system in macrophages and in monocytes as their source. Objective To examine whether the renin-angiotensin system is upregulated during the differentiation of monocytes to macrophages, and whether it is further regulated by angiotensin II and cytokines. Materials and methods We used a human leukemia cell line, THP-1, for monocytes. Differentiated THP-1, induced by adding phorbol 12-myristate 13-acetate for 24 h, were used as macrophages. Expression of messenger RNA of the renin-angiotensin system components was measured by quantitative reverse-transcriptase polymerase chain reaction. Angiotensin converting enzyme activity and subtype-specific angiotensin-binding sites of cultured cells, and angiotensin II production in the culture medium were measured. Results Macrophages expressed all components of the renin-angiotensin system except chymase. Cellular angiotensin converting enzyme activity and angiotensin II in the medium were increased 3.2- and 4.5-fold during differentiation, respectively. Expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors was increased 6.2-and 6.4-fold during differentiation, and was sustained for 7 days. Incubation with angiotensin II for 24 h caused downregulation of both AT1 and AT2 receptor messenger RNA, but the expression levels were still more than threefold higher compared with monocytes. The density of binding sites of AT1 and AT2 receptors in macrophages was 0.26 +/- 0.02 and 0.15 +/- 0.01 fmol/10(6) cells, respectively. Conclusion The renin-angiotensin system is markedly activated during monocyte/macrophage differentiation, and may participate in the development of atherosclerosis.

Blood pressure in adults after prenatal exposure to famine.

Abstract: BackgroundMany studies have shown that low birth weight is associated with high blood pressure The composition of the diet of pregnant women has also been found to affect blood pressure in their children We assessed the effect of prenatal exposure to the Dutch famine of 1944–1945, during which the

Vasopeptidase inhibition: a new concept in blood pressure management.

Abstract: Vasopeptidase inhibition is a new concept in cardiovascular therapy. It involves simultaneous inhibition with a single molecule of two key enzymes involved in the regulation of cardiovascular function, neutral endopeptidase (EC 24.11; NEP) and angiotensin-converting enzyme (ACE). Simultaneous inhibition of NEP and ACE increases natriuretic and vasodilatory peptides (including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP] of myocardial cell origin, and C-type natriuretic peptide [CNP] of endothelial cell origin) and increases the half-life of other vasodilator peptides including bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide system, vasopeptidase inhibitors (VPIs) reduce vasoconstriction and enhance vasodilation, thereby decreasing vascular tone and lowering blood pressure. Omapatrilat, a heterocyclic dipeptide mimetic, is a novel vasopeptidase inhibitor and a single molecule that simultaneously inhibits NEP and ACE with similar inhibition constants. Unlike ACE inhibitors, omapatrilat demonstrates antihypertensive efficacy in low-, normal-, and high-renin animal models. Unlike NEP inhibitors, omapatrilat provides a potent and sustained antihypertensive effect in spontaneously hypertensive rats (SHR), a model of human essential hypertension. In animal models of heart failure, omapatrilat is more effective than ACE inhibition in improving cardiac performance and ventricular remodeling and prolonging survival. Omapatrilat effectively reduces blood pressure, provides target-organ protection, and reduces morbidity and mortality from cardiovascular events in animal models. Omapatrilat is the first VPI to enter advanced USA clinical trials. Omapatrilat appears to be a safe, well-tolerated and effective antihypertensive in humans. Vasopeptidase inhibition is a novel and efficacious strategy for treating cardiovascular disorders, including hypertension and heart failure, that may offer advantages over currently available therapies.

Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia

Abstract: ObjectiveTo determine plasma levels of the endogenous bufodienolide Na+/K+ ATPase inhibitor, marinobufagenin-like factor (MBG), in normotensive pregnancy and in preeclampsia, to compare changes of MBG with that of ouabain-like compound (OLC), and to characterize the purified MBG immunoreactive facto

Recent weight gain in patients with newly diagnosed obstructive sleep apnea.

Abstract: ObjectivePatients with obstructive sleep apnea are often obese. Obesity may contribute to both sleep apnea itself and to the cardiovascular risk associated with sleep apnea. Weight loss in obese patients with sleep apnea may alleviate symptoms and decrease the severity of sleep apnea. Whether patien

Effects on blood pressure of drinking green and black tea.

Abstract: among those drinking green tea [5.5 mmHg (95%CI 21.4 to 12.4) and 3.1 mmHg (95%CI 20.1 to 6.3), respectively] and black tea [10.7 mmHg (95%CI 4.0 to 17.4) and 5.1 mmHg (95%CI 1.8 to 8.4), respectively]. The changes in blood pressure at 60 min were not significant. The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [increases of 1.7 mmHg (95%CI 21.6 to 5.0) and 0.9 mmHg (95%CI 21.3 to 3.1), respectively] or black tea [increase of 0.7 mmHg (95%CI 22.6 to 4.0) and decrease of 0.7 mmHg (95%CI 22.9 to 1.5), respectively] was not significant relative to caffeine.

Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age.

Abstract: Objective Epidemiological studies suggest that intrauterine growth restriction (IUGR) due to maternal undernutrition during pregnancy represents a major risk factor for hypertension and diabetes in adult age. However, placental insufficiency, rather than maternal malnutrition, is the main cause of IUGR in the Western world. We therefore studied the relationship between birth weight and adult blood pressure and glucose tolerance in an established animal model of placental insufficiency. Design IUGR was induced by uterine artery ligation in pregnant rats and the offspring were studied at 3-4 months of age. Methods In one subgroup of animals (n = 41, birth weight range 3.2-6.6 g) blood pressure was recorded over 72 h using telemetry and hypothalamic tissue levels of noradrenaline was measured. In another subgroup (n = 30, birth weight range 3.0-6.8 g) the activity of the sympathetic nervous system (SNS) was assessed by noradrenaline isotope dilution techniques and glucose tolerance determined by an intravenous glucose load. Results Adult blood pressure was independent of birth weight Haemodynamic responses of IUGR rats to moderate sound stress was unaltered. In male rats neither SNS activity, hypothalamic noradrenaline concentrations nor glucose tolerance was associated with birth weight In contrast, IUGR in female rats was associated with increased SNS activity, elevated fasting blood glucose as well as lower insulin and higher glucose levels in response to a glucose load. Conclusion IUGR is not linked to an elevated blood pressure at 3-4 months of age in this model. However, in female rats, IUGR is associated with increased SNS activity and impaired glucose tolerance in adult life.

Elevated systolic blood pressure as a risk factor for cardiovascular and renal disease.

Abstract: Aim To review published literature on the relationship between systolic blood pressure and risk of cardiovascular and renal disease. Data identification Studies were retrieved using the MEDLINE database, bibliographies, and the authors' reference files. Study selection Prospective cohort studies and randomized controlled trials which were published in English-language journals. Data extraction All retrieved publications were reviewed by the two authors. Information on sample size, duration, study design, antihypertensive medication, participant characteristics and outcomes was abstracted for randomized controlled trials which reported reductions in systolic blood pressure during intervention. Data synthesis Results from several prospective cohort studies indicate that the association between systolic blood pressure and risk of coronary heart disease, stroke and end-stage renal disease is continuous, graded, and independent. Furthermore, they suggest that the association of systolic blood pressure with these outcomes is stronger than that of diastolic blood pressure. Pooling of the data available from randomized controlled trials indicates that an average reduction of 12-13 mmHg in systolic blood pressure over 4 years of follow-up is associated with a 21% reduction in coronary heart disease, a 37% reduction in stroke, a 25% reduction in total cardiovascular mortality, and a 13% reduction in all-cause mortality. Conclusion Observational epidemiologic studies and randomized controlled trials have demonstrated that systolic blood pressure is an independent and strong predictor of risk of cardiovascular and renal disease.

Uric acid as a cardiovascular risk factor in arterial hypertension.

Abstract: BackgroundIncreased serum urate concentrations is a frequent finding in patients with hypertension. Since hyperuricaemia is associated with obesity, renal disease, hyperlipidaemia, and atherosclerosis the question as to whether serum urate is a cardiovascular risk factor per se has remained elusive.

The angiotensin type 2 receptor: variations on an enigmatic theme.

Abstract: Since its discovery and molecular characterization, the angiotensin AT 2 ,receptor has been enigmatic with respect to signalling pathways and function. Evidence now emerges that angiotensin II exerts actions through the AT 2 receptor which are directly opposed to those mediated by the AT 1 receptor. This can be exemplified e.g. by mutually antagonizing effects on cell growth. Upregulated by the endogeneous agonist itself, as well as by several growth-and differentiating factors in development and tissue injury, the AT 2 receptor appears to act as a modulator of complex biological programmes involved in embryonic development, cell differentiation, tissue protection and regeneration, as well as in programmed cell death. Research on the AT 2 receptor has thus unveiled hitherto unknown functions of the renin-angiotensin system extending far beyond the classical role of this old hormonal system in cardiovascular control.

Job strain, blood pressure and response to uncontrollable stress

Abstract: OBJECTIVE: The association between cardiovascular disease risk and job strain (high-demand, low-control work) may be mediated by heightened physiological stress responsivity. We hypothesized that high levels of job strain lead to increased cardiovascular responses to uncontrollable but not controllable stressors. Associations between job strain and blood pressure reductions after the working day (unwinding) were also assessed. DESIGN: Assessment of cardiovascular responses to standardized behavioral tasks, and ambulatory monitoring of blood pressure and heart rate during a working day and evening. PARTICIPANTS: We studied 162 school teachers (60 men, 102 women) selected from a larger survey as experiencing high or low job strain. METHODS: Blood pressure, heart rate and electrodermal responses to an externally paced (uncontrollable) task and a self-paced (controllable) task were assessed. Blood pressure was monitored using ambulatory apparatus from 0900 to 2230 h on a working day. RESULTS: The groups of subjects with high and low job strain did not differ in demographic factors, body mass or resting cardiovascular activity. Blood pressure reactions to the uncontrollable task were greater in high than low job-strain groups, but responses to the controllable task were not significantly different between groups. Systolic and diastolic blood pressure did not differ between groups over the working day, but decreased to a greater extent in the evening in subjects with low job strain. CONCLUSIONS: Job strain is associated with a heightened blood pressure response to uncontrollable but not controllable tasks. The failure of subjects with high job strain to show reduced blood pressure in the evening may be a manifestation of chronic allostatic load.

Vascular wall function as a risk marker for cardiovascular disease.

Abstract: Elevated systolic blood pressure (SBP) and wide pulse pressure (PP) are both important risk markers for cardiovascular disease. They are indicative of a vascular abnormality, most likely located at the endothelial-vascular interface, where the balance between vasodilator and vasoconstriction determines vascular tone, structure and change in blood pressure. This abnormality makes vessel walls vulnerable to degeneration. Reducing blood pressure in patients with endothelial-vascular dysfunction has been found to reduce the rates of cardiovascular events. Preliminary data also suggest that drug therapy has successfully improved endothelial dysfunction. Endothelial release of nitric oxide has little effect on the aorta, but affects the elasticity of thinner-walled branch vessels and arterioles beneficially. Nitric oxide is normally released in response to increased blood flow and this process is often impaired by various disease states. Since blood flow can be measured, endothelial function can be assessed. Arterial compliance can be determined clinically by a technique that combines pulse wave recording and computer analysis of diastolic decay. In certain disease states, compliance seems to be reduced more in smaller vessels, a marker of early stage vascular disease. Screening for arterial elasticity with this tool can identify those patients with early stages of arterial wall disease and prevent further damage. However, further research is needed to determine whether the benefit lies in lowering blood pressure or in the actual effect of the drug in restoring the function of the arterial wall.

Clinical value of ambulatory blood pressure monitoring.

Abstract: UNLABELLED 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 EQUIPMENT: Important 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 PROGNOSIS: White-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 CYCLE: One 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 SYSTEM: The 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 SYSTEM: Almost 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 SYSTEM: Non-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. DIABETES BP 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 USES: The 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.

Ageing and hypertension: the assessment of blood pressure indices in predicting coronary heart disease.

Abstract: Objective To determine whether pulse pressure (PP), diastolic blood pressure (DBP), systolic blood pressure (SBP), or mean arterial pressure (MAP) is the superior haemodynamic predictor for the risk of coronary heart disease (CHD). Methods Age-related changes of blood pressure in normotensive and untreated hypertensive subjects in a population-based cohort from the Framingham Heart Study were characterized. The relationship between these blood pressure indices and risk of CH D over a 20-year follow-up period were then evaluated. Results There was a parallel linear rise in SBP, DBP and MAP from age 30-49 years, suggesting increased peripheral vascular resistance (PVR) in this age group. After age 50-60 years, DBP declined, PP rose steeply, and MAP levelled off, while SBP continued to show a linear increase, suggesting increasing predominance of large artery stiffness (LAS) in this middle-aged and elderly group. After adjusting for age, sex and other risk factors, MAP and DBP consistently underestimated PVR and risk of CHD. Systolic blood pressure fully represented PVR but frequently underestimated LAS and risk of CHD. Pulse pressure was superior to SBP as a surrogate marker for LAS and predictor of CHD risk in the presence of discordantly low DBP, but PP frequently underestimated PVR. Conclusions In middle-aged and older subjects, at any given level of SBP > or = 120 mmHg, the risk of CHD rose with discordantly lower DBP, suggesting that the wider PP was driving the risk for CHD. These results suggest that total haemodynamic load, defined as the sum of pulsatile load (LAS) and steady-state load (PVR), is a major determinant of CHD risk.

Sympathetic tone restrains arterial distensibility of healthy and atherosclerotic subjects.

Abstract: Background Sympathetic activation induced by cold pressor test or cigarette smoking is accompanied by a marked reduction of radial artery distensibility. It is not known, however, whether arterial distensibility is under tonic sympathetic restraint, or whether this restraint involves arteries greater than the radial one in both normal and pathological conditions. Methods We studied the distensibility of radial artery by continuous ultrasonographic assessment of the changes in arterial diameter over the diasto-systolic pressure range (finger pressure measurement) in eight patients with a Dupuytren disease before and 20 min after ipsilateral brachial plexus anaesthesia. We also studied ultrasonographic distensibility of femoral artery in seven subjects before and 20 min after ipsilateral subarachnoid anaesthesia, performed before arthroscopic surgery, and in five patients with claudicatio intermittens before and 1 month after ipsilateral removal of the lumbar sympathectomy chain. In all three conditions, the contralateral artery served as control. Results The three interventions did not cause any significant alteration in blood pressure and heart rate. Radial artery distensibility was markedly increased by ipsilateral anaesthesia of the brachial plexus (+36%, P < 0.01). This was the case also for femoral artery distensibility both following ipsilateral subarachnoid anaesthesia in healthy subjects (+47%, P< 0.05) or ipsilateral sympathetic gangliectomy in patients with peripheral artery disease (+26%, P< 0.05). In all three instances, the distensibility of the contralateral artery remained unaffected. Conclusions These data indicate that the sympathetic nervous system exerts a marked tonic restraint of arterial distensibility. This restraint involves medium-size and large muscular arteries and can also be seen in subjects with peripheral artery disease. This stiffening influence may increase the traumatic effect of intravascular pressure on the vessel wall and favour atherosclerosis.

Losartan inhibits the post-transcriptional synthesis of collagen type I and reverses left ventricular fibrosis in spontaneously hypertensive rats.

Abstract: ObjectivePrevious studies have shown that as well as left ventricular hypertrophy, myocardial fibrosis develops early in rats with spontaneous hypertension (SHR). The present study was designed to investigate whether chronic treatment with the angiotensin II type 1 (AT1) receptor antagonist losartan

Angiotensin II stimulates DNA and protein synthesis in vascular smooth muscle cells from human arteries: role of extracellular signal-regulated kinases.

Abstract: Objective: This study investigates the growth effects and associated signaling pathways of angiotensin II (Ang II) in human vascular smooth muscle cells. Methods: Cultured vascular smooth muscle cells derived from resistance arteries ( Results: Ang II dose-dependently increased 3H-thymidine incorporation in cells from aorta (Emax = 276 ± 10.4% of control) and resistance arteries (Emax = 284 ± 5.1% of control). Ang II also stimulated 3H-leucine incorporation in cells from aorta (Emax = 162 ± 11.6 of control) and resistance arteries (Emax 175 ± 10% of control). Unlike Ang II, endothelin-1 failed to significantly alter cellular growth, except at high concentrations (> 10-7 mol/l), where it had a weak stimulatory effect. Losartan, but not PD123319, blocked Ang II-stimulated growth responses. Ang II significantly increased phosphorylation of ERK-1 and ERK-2, with maximum responses obtained at 5 min. PD98059 inhibited Ang II-stimulated ERK activity and abrogated agonist-induced DNA and protein synthesis. Losartan, but not PD123319 inhibited Ang II-induced phosphorylation of ERK-1 and ERK-2. Conclusions: Ang II stimulates both hyperplasia and hypertrophy in vascular smooth muscle cells from human arteries. These growth effects are mediated via Ang II receptors of the AT1 subtype that are linked to ERK-dependent signaling pathways.

A population study of ethnic variations in the angiotensin-converting enzyme I/D polymorphism: relationships with gender, hypertension and impaired glucose metabolism.

Abstract: Background The 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. Objective To 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.

Increased cardiovascular mortality in hypertensive patients with renal artery stenosis. Relation to sympathetic activation, renal function and treatment regimens.

Abstract: BackgroundPrevious studies in hypertensive patients with renovascular disease have shown both elevated sympathetic nerve activity and increased cardiovascular mortality.ObjectiveThe aim of the present study was to assess long-term survival in hypertensive patients with renal artery stenosis in relat

Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.

Abstract: OBJECTIVE Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

Characteristics of blood pressure measured at home in the morning and in the evening: The Ohasama study

Abstract: ObjectiveTo determine the qualitative and quantitative differences of blood pressure measured at home (home measurement) in the morning versus the evening.MethodsOf 3744 participants, aged 20 years or older in the Ohasama population, more than 14 home measurements in the morning and in the evening,