Current Hypertension Reviews - Volume 3, Issue 4, 2007

Normal pregnancy is associated with changes in the cardiovascular system, including vascular remodeling of the uterine and systemic circulation in order to meet the metabolic demands of the developing fetus. These cardiovascular changes are due to alterations in the amount/activity of vascular mediators such as nitric oxide, prostacyclin and endothelin in the endothelium; calcium and protein kinase C in the smooth muscle; and metalloproteases in the extracellular matrix. Hypertension in pregnancy is a major complication, and can lead to life threatening neurovascular disorders. It has been suggested that hypertension in pregnancy may develop from an inadequate invasion of cytotrophoblasts into the uterine artery, causing reduction in the uteroplacental perfusion pressure, and resulting in placental ischemia/hypoxia. This placental hypoxic state is thought to induce the release of various biologically active factors such as cytokines, reactive oxygen species, and hypoxia-inducible factors. Elevated plasma/tissue levels of these factors during pregnancy could cause vascular dysfunction, vasoconstriction and hypertension. The purpose of this review is to discuss the interactions between biologically active circulating factors and vascular mediators, released during preeclampsia as compared to those released in other conditions characterized by hypoxia, in order to provide insight into the sequence of events that leads to the development of hypertension in pregnancy.

Hypertension has been associated with both decreased production of the potent vasodilator nitric oxide (NO) and vascular remodeling. L-arginine is the substrate for endogenous NO production by the NO synthases (NOS). Larginine is also the substrate for the arginases, which metabolize L-arginine to L-ornithine and urea. There are 2 described isoforms of arginase, arginase I and arginase II; both isoforms are inducible and widely expressed in the body. Recently, it has been found that arginase I and II are expressed in vascular tissue, and that arginase activity can be induced by many hypertensive stimuli, including chronic inflammation and salt loading. Induction of arginase activity results in decreased L-arginine bioavailability to NOS and thereby may decrease the endogenous production of NO in the vasculature. Furthermore, L-ornithine produced by arginase can be further metabolized to polyamines and proline, which are central to vascular smooth muscle cell proliferation and vascular remodeling. Thus, arginase is involved in the pathogenesis of hypertension by promoting vascular remodeling and attenuating the endogenous production of NO. This review will examine the regulation of arginase expression and its role in the pathogenesis of hypertension, as well as the therapeutic potential of arginase inhibition for treating some forms of hypertension.

In recent years, some epidemiological studies reported that coffee consumption was associated with increased in serum cholesterol and blood pressure and subsequently increased cardiovascular risk. Coffee is one of the most popular beverages consumed in a large amount in Western Countries. Coffee beverages contain several hundred different substances, but its effects of coffee on cardiovascular system have been mainly related to caffeine. Caffeine is present in a number of dietary sources consumed worldwide i.e. tea, coffee, cocoa beverages, chocolate bars and soft drinks. Caffeine exerts various effects on the autonomic nervous system and on blood vessels. It is well-known that a dietary intake and lifestyle play an important role in hypertension. Meta-analyses of randomized control trials that examined the effects of coffee and caffeine intake on blood pressure presented conflicting results. Shortterm administration of caffeine in non-coffee drinkers increases blood pressure, plasma renin activity, and catecholamines. Heavy coffee drinkers seem to have negative effects mainly due to the activation of sympathetic system, i.e. rise in blood pressure, increase of risk of develop coronary artery disease. On contrary a moderate consumption shows no detrimental effects on cardiovascular system. In addition habitual coffee drinkers have less sympathetic response. Recent studies underling the antioxidants properties of coffee due to different compounds.

Physical activity is a cost-effective way to decrease blood pressure since it possesses potential for having a major public health impact. Prospective studies, have demonstrated that moderate-to-vigorous intensity physical activity at baseline seem to be associated with a lower incidence of hypertension among white men regardless of body mass index. The data among women are controversial. Further, there is not enough evidence at this moment to conclude that high commuting or occupational physical activity would be associated with a reduced risk for incident hypertension. Intervention studies however, have demonstrated that increased physical activity reduces systolic and diastolic blood-pressure in hypertensive and normotensive individuals independently from weight loss. In light of the evidence from these studies, physical activity should be practiced at a moderate intensity level (min. 40% of VO2 max) three times per week and for session times of at least 30 minutes in order to reduce systolic and diastolic blood pressure. Thus, physical activity should be considered as an important measure for the prevention and treatment of hypertension. Physical activity is a costeffective way to decrease blood pressure since it possesses potential for having a major public health impact.

Background: Asian Indians account for one-fifth of all cardiovascular deaths worldwide. It is well known that hypertension is a major risk factor for cardiovascular mortality and morbidity, but there has been no national survey for estimating the prevalence of hypertension in the Indian population. Hypertension in this ethnic group is less well studied than hypertension in blacks or Caucasians. Methods: We searched PubMed and MEDLINE using the words “Asian Indians” “hypertension” “blood pressure” “epidemiology” “prevalence” “prevention” “treatment” as search items and went through the major Indian journals to gather sufficient data regarding hypertension in Asian Indians. Most of the data was acquired from studies conducted in India, as there are only limited studies on Indians who have settled overseas. Results: High prevalence of hypertension was found in the urban Indian population as compared to the rural Indian population, while there was inconsistent data on migrant Indians. The modern Indian diet and lifestyle may be responsible for the urban - rural differences. Large proportion of Indian population is unaware of their condition and significant proportion of them is pre-hypertensive. No specific treatment guidelines for this ethnic group are available. Conclusion: The escalating incidence of hypertension among Asian Indians in urban India is alarming. This will likely add to the already existing cardiovascular disease burden in this ethnic group and it is imperative to conduct additional epidemiological and clinical studies to assess the prevalence, pathogenesis, and optimal pharmacotherapy of hypertension in Asian Indians. Aggressive screening and treatment regimen should be adopted considering the risk of untreated and sub-optimally treated hypertension and specific guidelines for treatment of hypertension in Asian Indians appears warranted.

The potential role of genetic variations in the pathogenesis of cardiovascular diseases is a field of continuous investigation and the perception of the role of genes has dramatically changed during the last 20 years. The two more commonly used experimental designs, based on a candidate gene or a genome wide approach, have been somehow replaced by the possibility to build haplotypes in the context of a single gene using a so-called gene-wide approach. Human diseases, however, are far from theoretical and in silico speculation and the analysis of the contribution of the individual genetic background to their pathogenesis still needs a working hypothesis that, starting from the patho-physiology of the disease under investigation, takes advantage of the newly available technologies and software. In this perspective, the gene-wide approach may represent an attractive methodology to bridge the gap between bench and bedside. Here we review the rationale behind this approach, the available methodologies and the potential clinical applications.

Renal ischaemia due to renal artery stenosis (RAS) may be the cause of end-stage renal failure in a growing number of patients. In recent years, decisions taken on the optimal management of patients with renal artery stenosis have sparked controversy and debate among cardiologists, internists and nephrologists. The main reason underlying the ongoing controversy may be the heterogeneity of clinical entities that are normally grouped together through the use of the umbrella term renal artery stenosis. Actually, when thinking of renal artery stenosis our view is still deeply shaped by Goldblatt's seminal study. Yet it should be remembered that in Goldblatt's experiment renal artery clipping occurred in the context of a perfectly healthy vascular tree. A clinical situation that comes close to Goldblatt's experiment is the one in which the stenosis mainly, if not exclusively, affects the renal artery in relatively young subjects whose vascular tree is not badly damaged. In clinical practice, this situation is frequently encountered in subjects bearing fibromuscular dysplasia (FMD), non-ostial or truncal stenosis (Tru-RAS), and stenosis of the transplanted kidney (TRAS). Contrariwise, ostial stenosis is more precisely a lesion of the thickened aortic wall that encroaches upon the renal artery ostium, rather than a lesion in the renal artery itself. Hence, the reference paradigm ought not to be Goldblatt's model but rather more complex models in which the narrowing of the renal artery is associated to other factors, such as a high cholesterol diet, smoking or aging. The causes of renal impairment are likely to be different in the two situations. In pure renal artery stenosis (FMD, TruRAS, TRAS), the decrease in GFR is mainly caused by hypoperfusion secondary to stenosis, which is then reversible after revascularization, while in subjects with ostial stenosis and/or in older subjects with a badly injured aorta the pathogenesis is multifactorial, with intrarenal atheroma, cholesterol embolism and ischaemic damage all making a contribution. This may account for the lack of correlation between the degree of stenosis and the entity of renal impairment, as well as the low rate of renal function recovery in subjects with ostial stenosis. In our view, keeping the different entities separate enables clinicians to take the right decision on revascularization.

Essential hypertension research faces daunting hurdles in gene identification and elucidating mechanisms underlying gene-gene interactions and genome regulations. Recent discoveries in experimental models of polygenic hypertension have revealed the genetic architecture and a functional hierarchy of genes influencing BP. These findings are potentially shedding new conceptual lights on complex genetic mechanisms controlling essential hypertension. Seemingly ‘conflicting’ results in association studies of candidate genes with essential hypertension may be interpreted by their inherent genetic property of population specificity. A lack of detection of genes demonstrating major BP effects may be attributed to the masking and compounding effects of genetic heterogeneity, among other factors, present among human subjects. The future research can be greatly benefited from combining animal model studies with human population-based analyses, i.e. translating the discovery in experimental models into humans, and conversely, validating human findings via animal model investigations.