Current Hypertension Reviews - Volume 4, Issue 2, 2008

Microparticles are small membrane vesicles released from the plasma membrane into the extracellular space by different cell types both in vivo and in vitro. Formation of microparticles is a part of normal cellular function, but it is increased in many diseases accompanied by endothelial cell dysfunction. This review summarizes the mechanisms of microparticle formation and the role of circulating endothelial microparticles in the development of endothelial cell dysfunction. This article also discuss the recent advances in microparticle research in cardiovascular diseases.

The concept that atherosclerosis is an inflammatory disease is well established. Low-grade inflammation, enhanced oxidant stress and lipid peroxidation have been shown in association with increased cardiovascular risk associated with cardiovascular events. Arterial hypertension represents one of the most common conditions associated with increased cardiovascular risk, including stroke, myocardial infarction and heart failure. Endothelial dysfunction was initially identified as impaired vasodilation to specific stimuli; nonetheless, it has recently been suggested that the term ‘endothelial dysfunction’ would include not only reduced vasodilation, but also a proinflammatory and prothrombotic state. Inflammation has also been associated with decreased endothelium-dependent relaxation, a process related to an alteration in the bioavailability of nitric oxide. Biomarkers may yield information on outcome of disease as measurable endpoints related to specific disease. There is considerable evidence that both endothelial dysfunction and inflammation are associated with most forms of cardiovascular disease, such as essential hypertension. Besides, experimental evidence indicates that oxidative stress contributes to the pathogenesis of hypertension and may be involved in the process of atherogenesis. This review will focus on recent clinical studies on the relationship of arterial hypertension with a few molecules considered as biomarkers of oxidative stress, inflammation and endothelial dysfunction.

Although the large majority of patients with end-stage renal disease are hypertensive, blood pressure levels are insufficiently controlled despite the complex pharmacological treatment they receive. Hypertension is known to be associated with cardiovascular complications, but its impact on mortality is still controversial. The paradox of “reverse epidemiology”, i.e. better survival of dialysis patients with high blood pressure levels, is common to other patients, such as those with heart failure, and is linked to the left ventricular abnormalities that are found in many hemodialysis (HD) patients. Moreover, unlike epidemiological studies on the general population, observational surveys on HD patients have been performed for shorter periods of time. After correction for confounders and over the long-term, hypertension seems to be an independent risk factor for mortality in HD patients and is multi-factorial in origin. Several causes are recognized: volume overload, sympathetic hyperactivity, activation of the renin angiotensin system, vascular calcification and erythropoietin treatment. The optimal blood pressure target seems to be pre-dialysis values of 140/90 mmHg, or the lowest possible values which are well tolerated during the dialysis session. The best method for assessing blood pressure levels remains to be established, because of oscillations in relation to the dialysis session or the inter-dialysis period. Home blood pressure measurement seems to be as sensitive as ambulatory blood pressure monitoring; alternatively the average of 12 predialysis measurements has been used. Drug treatment is unsatisfactory, and difficult kinetics and side effects are often reported. Several non pharmacological options are available, such as modifications to the hemodialysis schedule, increased HD efficiency, and use of biocompatible membranes, besides dietary salt and fluid restriction. A correct approach to HD can efficiently reduce the incidence of hypertension, cardiovascular complications and mortality rate in these patients.

This review addresses the role of hypertension in precipitating Calcific aortic valve disease (CAVD) and the therapeutic potential of anti-hypertensive interventions to ameliorate CAVD. CAVD was originally considered to be a degenerative disease representing the “wear and tear” of the aortic valves. More recently both conceptually and experimentally, CAVD has come to be considered the result of an active disease process. Whilst, there are some common factors in the pathology and risk factors for atherosclerosis and CAVD there are also some distinct differences. Hypertension is an established risk factor for coronary artery disease and has been recognised as a risk factor for CAVD. Angiotensin converting enzyme inhibitors have been found to have beneficial effects in CAVD and as in atherosclerosis such effects may be due to the blood pressure lowering action but also to direct pleiotropic effects on the biochemical and cellular mechanisms of disease progression in the respective tissues. The very high prevalence of hypertension in the community coupled with an aging population, a risk factor associated with both hypertension and CAVD, infers that hypertension will be one of the predominant factors that increase the impact of CAVD on human health in the coming decades.

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment.

Obesity, hypertension, and obesity-related hypertension are rapidly growing public health problems. Heightened sympathetic nerve activity is well-established observations in obesity and hypertension. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the β2 and β3-adrenergic receptors in humans. Further, β-adrenoceptors importantly influence vascular reactivity and insulin resistance. Obesity and hypertension have a strong genetic determinant. Genetic polymorphisms of the β- adrenoceptor gene have been shown to alter the function of β2- and β3-adrenoceptor subtype and thus to modify the response to sympathetic nerve activity (catecholamines). Among β2-adrenoceptor polymorphisms, Arg16Gly and Gln27Glu are considered the most functionally important in relation to obesity and hypertension. Genetic variations in the β3- adrenoceptor, such as the Try64Arg variant, are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of β2- and β3-adrenoceptor genes with obesity and hypertension have been conflicting. Focusing on the relationships between the sympathetic nervous system and β2- and β3-adrenoceptor polymorphisms in obesity and hypertension might help to understanding these conflicting findings. The purpose of this article is to provide the current findings on the relationships between β-adrenoceptor polymorphisms, obesity, and hypertension including our own findings.

In recent years, much more insight is given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH), that currently represents one of the most severe events during the HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnoea that will progress to the point of breathlessness at rest. Echocardiography has been proved to be an extremely useful tool for the diagnosis of HRPH, and Doppler echocardiography may be used to estimate systolic pulmonary artery pressure, and to monitor the effects of therapy. Assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating the response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension, since vasoconstriction is a determinant characteristic of this disease. More recently, more effective therapies for pulmonary arterial hypertension have been available, including prostanoids, endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, allowing an amelioration of symptoms and a better prognosis. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new efficient antiretroviral treatment will be introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV-infected patients in the future.

Age- and lifestyle-related arterial stiffening is a well-established independent cardiovascular risk factor. Previous studies have investigated the effects of exercise training on arterial stiffness. Aerobic exercise training reduces arterial stiffness. On the other hand, muscle-strengthening exercise, such as weight training, may stiffen central elastic arteries. However, the mechanism underlying exercise training-associated changes in arterial stiffness has not been fully elucidated. Adaptations of arteries to exercise training may, at least partly, be regulated by local factors. We have focused on endothelium-derived vasoactive factors, such as nitric oxide (NO) and endothelin (ET)-1, because the endothelium regulates vascular tone. NO has a significant vasodilatory effect, and ET-1 is a potent vasoconstrictor. Both factors have been reported to be affected by exercise training. This article reviews literature investigating the effects of exercise training on arterial stiffness and the role of endothelium-derived factors. We discuss here the role of endothelial function in exercise training-induced changes in arterial stiffness.