Variabilité des concentrations plasmatiques de l'angiotensinogène et risque d'hypertension artérielle chez le rat transgénique [Variability of plasma angiotensinogen levels and risk of hypertension in a transgenic rat model].

AIM: Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors. METHODS: Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n=3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction). RESULTS: At baseline, transgenic rats had +18mmHg higher bood pressure and -8% lower body weight compared to non-transgenic rats (P<0.05) without significant changes for the vehicle groups throughout the study (P>0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P<0.05) in transgenic and +25%, +5.3% and +6.7% (P>0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P>0.05). CONCLUSION: Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.

The metabolic syndrome in hypertension: European society of hypertension position statement.

The metabolic syndrome considerably increases the risk of cardiovascular and renal events in hypertension. It has been associated with a wide range of classical and new cardiovascular risk factors as well as with early signs of subclinical cardiovascular and renal damage. Obesity and insulin resistance, beside a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with proinflammatory properties, have been implicated in the pathogenesis. The close relationships among the different components of the syndrome and their associated disturbances make it difficult to understand what the underlying causes and consequences are. At each of these key points, insulin resistance and obesity/proinflammatory molecules, interaction of demographics, lifestyle, genetic factors, and environmental fetal programming results in the final phenotype. High prevalence of end-organ damage and poor prognosis has been demonstrated in a large number of cross-sectional and a few number of prospective studies. The objective of treatment is both to reduce the high risk of a cardiovascular or a renal event and to prevent the much greater chance that metabolic syndrome patients have to develop type 2 diabetes or hypertension. Treatment consists in the opposition to the underlying mechanisms of the metabolic syndrome, adopting lifestyle interventions that effectively reduce visceral obesity with or without the use of drugs that oppose the development of insulin resistance or body weight gain. Treatment of the individual components of the syndrome is also necessary. Concerning blood pressure control, it should be based on lifestyle changes, diet, and physical exercise, which allows for weight reduction and improves muscular blood flow. When antihypertensive drugs are necessary, angiotensin-converting enzyme inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel blockers are preferable over diuretics and classical beta-blockers in monotherapy, if no compelling indications are present for its use. If a combination of drugs is required, low-dose diuretics can be used. A combination of thiazide diuretics and beta-blockers should be avoided.

Hypertension. Angio-oedème sous inhibition de l'enzyme de conversion de l'angiotensine et de la dipeptidyl-peptidase-4 [Angioedema during ACE and DPP-4 inhibition]

Angioedema is a rare side effect of angiotensin converting enzyme (ACE) inhibitors. Its cause is probably related to the accumulation of bradykinin and substance P, i.e. two proinflammatory peptides normally inactivated by ACE. Angioedema occurs most of the time at the early phase of treatment, but may also develop during long-term treatment. It might involve the gastro-intestinal tract, leading to abdominal pain, vomiting and/or diarrhea, as well as pancreatitis. Dipeptidyl-ptidase-4 (DPP-4) is another enzyme allowing the degradation of bradykinin and substance P. Co-administering an ACE inhibitor and a DPP-4 inhibitor (as an antidiabetic agent) increases significantly the risk of angioedema.

Hypertoniebehandlung bei Nierenarterienstenose [Hypertension therapy in patients with renal artery stenosis].

Renovascular hypertension is due to reduced renal parenchymal perfusion. The correct diagnosis can be difficult. It is important to note that the demonstration of renal artery stenosis in a patient with hypertension does not necessarily constitute renovascular hypertension. Often, clinically nonsignificant and asymptomatic renal artery stenosis are found in patients with essential hypertension, or renal failure of other origin. Renovascular disease is a complex disorder with various clinical presentations. In patients with significant renovascular hypertension plasma renin is increased. For this reason the therapy aims to block the renin-angiotensin-aldosterone system. Bilateral renal artery stenosis causes renal sodium retention. In this situation a diuretic drug has to be added to the therapy. Endovascular or surgical therapy has to be considered in patients with flash pulmonary edema or fibromuscular dysplasia. The control of cardiovascular risk factors is important.

Upward hypertension trends: changes in blood pressure or in antihypertensive treatment?

Comment on: Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 1999-2004. Hypertension. 2008 Nov;52(5):818-27. PMID: 18852389.

Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE).

OBJECTIVES: Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated.METHODS : A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed.RESULTS : Data from 1376 patients were available. Mean age was 65 +/- 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (<140/90 mm Hg for uncomplicated and <130/80 mm Hg for complicated hypertension) was achieved in 48.9%. Compared to patients with complicated hypertension, BP control was better in patients with uncomplicated hypertension (59.4% vs. 19.2%, p < 0.001). As a monotherapy the most prescribed drug class were angiotensin receptor blockers (ARB, 41%), followed by angiotensin converting enzyme (ACE) inhibitors (21.5%), betablockers (20.8%) and calcium channel blockers (CCB, 10.8%). The most prescribed drug combinations were ARB + diuretic (30.1%) and ACE inhibitors + diuretic (15.3%). 46% were receiving a fixed drug combination. In only 32.7% of patients with uncontrolled hypertension was a change in drug therapy made.CONCLUSION : This representative survey on treated adult hypertensive patients shows that, compared to earlier reports, the control rate of hypertension has improved in Switzerland for uncomplicated but not for complicated, particularly diabetes-associated hypertension. ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy, whereas diuretics and ARBs were the most used for combination therapy.

L'hypertension chez les transplantés d'organes [Hypertension in solid organ transplants].

Hypertension is highly prevalent in transplantation and affects all type of organs. With the introduction of calcineurin inhibitors as immunosuppressive drugs, acute allograft rejection episodes have been significantly reduced and hence patient and allograft survival rates have dramatically improved. However, cardiovascular complications have become an important cause of morbidity and mortality. Treating cardiovascular risk factors such as diabetes, dyslipidemia and hypertension seems obvious, however in this population, there is little evidence for specific blood pressure targets, or for the best strategy to achieve blood pressure control. The aim of this article is to review the epidemiology and physiopathology of hypertension in transplant recipients as well as its clinical management.

Revisiting sodium and water reabsorption with functional genomics tools.

PURPOSE OF REVIEW: The kidney plays an essential role in maintaining sodium and water balance, thereby controlling the volume and osmolarity of the extracellular body fluids, the blood volume and the blood pressure. The final adjustment of sodium and water reabsorption in the kidney takes place in cells of the distal part of the nephron in which a set of apical and basolateral transporters participate in vectorial sodium and water transport from the tubular lumen to the interstitium and, finally, to the general circulation. According to a current model, the activity and/or cell-surface expression of these transporters is/are under the control of a gene network composed of the hormonally regulated, as well as constitutively expressed, genes. It is proposed that this gene network may include new candidate genes for salt- and water-losing syndromes and for salt-sensitive hypertension. A new generation of functional genomics techniques have recently been applied to the characterization of this gene network. The purpose of this review is to summarize these studies and to discuss the potential of the different techniques for characterization of the renal transcriptome. RECENT FINDINGS: Recently, DNA microarrays and serial analysis of gene expression have been applied to characterize the kidney transcriptome in different in-vivo and in-vitro models. In these studies, a set of new interesting genes potentially involved in the regulation of sodium and water reabsorption by the kidney have been identified and are currently under detailed investigation. SUMMARY: Characterization of the kidney transcriptome is greatly expanding our knowledge of the gene networks involved in multiple kidney functions, including the maintenance of sodium and water homeostasis.

Low utilization of health care services following screening for hypertension in Dar es Salaam (Tanzania): a prospective population-based study.

BACKGROUND: Drug therapy in high-risk individuals has been advocated as an important strategy to reduce cardiovascular disease in low income countries. We determined, in a low-income urban population, the proportion of persons who utilized health services after having been diagnosed as hypertensive and advised to seek health care for further hypertension management. METHODS: A population-based survey of 9254 persons aged 25-64 years was conducted in Dar es Salaam. Among the 540 persons with high blood pressure (defined here as BP >or= 160/95 mmHg) at the initial contact, 253 (47%) had high BP on a 4th visit 45 days later. Among them, 208 were untreated and advised to attend health care in a health center of their choice for further management of their hypertension. One year later, 161 were seen again and asked about their use of health services during the interval. RESULTS: Among the 161 hypertensive persons advised to seek health care, 34% reported to have attended a formal health care provider during the 12-month interval (63% public facility; 30% private; 7% both). Antihypertensive treatment was taken by 34% at some point of time (suggesting poor uptake of health services) and 3% at the end of the 12-month follow-up (suggesting poor long-term compliance). Health services utilization tended to be associated with older age, previous history of high BP, being overweight and non-smoking, but not with education or wealth. Lack of symptoms and cost of treatment were the reasons reported most often for not attending health care. CONCLUSION: Low utilization of health services after hypertension screening suggests a small impact of a patient-centered screen-and-treat strategy in this low-income population. These findings emphasize the need to identify and address barriers to health care utilization for non-communicable diseases in this setting and, indirectly, the importance of public health measures for primary prevention of these diseases.

Les antagonistes des récep- teurs de l'endothéline ont-ils une place dans le traitement de l'hyper- tension artérielle [Do endothelin receptors antagonists have a place in the treatment of arterial hypertension?].

The discovery in 1988 of endothelin, the most potent human endogenous vasoconstrictor, has opened the race to the discovery of a new weapon against arterial hypertension. The development of the endothelin receptors antagonists (ERAs) and the demonstration of their efficacy in preclinical models initially raised a wave of enthusiasm, which was however tempered due to their unfavorable side effect profile. In this article we will review the phases of the development ERAs, and their current and future place as therapeutic tool against arterial hypertension.

ESH-ESC guidelines for the management of hypertension.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.