Development Of Hypertension Disease Research Articles

Placental Volume and Uterine Artery Doppler in Pregnancy Following In Vitro Fertilization: A Comprehensive Literature Review.

The number of pregnancies achieved using in vitro fertilization (IVF) is rapidly increasing around the world. The chance of obtaining a successful pregnancy is also significantly improved due to technological advances and improvement in infertility treatment. Despite this success, there is evidence that pregnancy conceived by IVF has an increased risk of adverse maternal and perinatal outcome mainly represented by the development of hypertensive diseases, pre-eclampsia, and fetal growth restriction. Although different cofactors may play a role in the genesis of these diseases, the development of the placenta has a pivotal function in determining pregnancy outcomes. Advances in ultrasound technology already allows for evaluation in the first trimester, the impedance to flow in the uterine artery, and the placental volume using Doppler and three-dimensional techniques. This review article aims to describe the modification occurring in placental volume and hemodynamics after IVF and to summarize the differences present according to the type of IVF (fresh vs. frozen-thawed embryos).

Clues and new evidences in arterial hypertension: unmasking the role of the chloride anion.

The present review will focus on the role of chloride anion in cardiovascular disease, with special emphasis in the development of hypertensive disease and vascular inflammation. It is known that acute and chronic overload of sodium chloride increase blood pressure and have pro-inflammatory and pro-fibrotic effects on different target organs, but it is unknown how chloride may influence these processes. Chloride anion is the predominant anion in the extracellular fluid and its intracellular concentration is dynamically regulated. As the queen of the electrolytes, it is of crucial importance to understand the physiological mechanisms that regulate the cellular handling of this anion including the different transporters and cellular chloride channels, which exert a variety of functions, such as regulation of cellular proliferation, differentiation, migration, apoptosis, intracellular pH and cellular redox state. In this article, we will also review the relationship between dietary, serum and intracellular chloride and how these different sources of chloride in the organism are affected in hypertension and their impact on cardiovascular disease. Additionally, we will discuss the approach of potential strategies that affect chloride handling and its potential effect on cardiovascular system, including pharmacological blockade of chloride channels and non-pharmacological interventions by replacing chloride by another anion.

Hypervetilation syndrome as a risk factor of diastolic dysfunction among hypertension patients

Hypertensive disease is one of the urgent problems in the modern cardiology. It is known that a huge variety of comorbid states influence the development of hypertensive disease, i. e. neurogenic hyperventilating syndrome. It is the sign and the marker of suprasegmental vegetative structures disorders that destabilize homeostasis, initiate the development of specific pathological processes, which are the base of somatization of hyperventilating disorders, including heart disorders. It led to research of structural and functional characteristics of the ventricles with the help of echocardiology among hypertensive patients with neurogenic hyperventilating syndrome. Ventricular dilation of cavities, mostly of the right one without thickening of the walls, was found in the patients with stage 1 hypertension disease (43.59 %). Dilation of the ventricular cavities was also revealed in hypertensive patients with stage 2 hypertension disease in 37.88% of cases. The next variations of remodeling were registered: concentric – in 10.61% of cases; concentric hypertrophy – in 22.73%; asymmetric hypertrophy – in 12.12%; eccentric remodeling and eccentric hypertrophy of the left ventricle – in 4.55% and 9.09% of patients, respectively. Thickening of the right ventricle wall was observed in 13.64% of patients. In the control group of patients without hypertonic syndrome, the signs of concentric and asymmetric hypertrophy were noticed in 10% of patients, eccentric – in 20%; extension of the left ventricle – in 20%. The assessment of the condition of transmitral and tricuspid flows revealed a significant increase in the number of cases, disorders, relaxation of the heart ventricles among hypertensive patients with neurogenic hyperventilating syndrome. It can be a sign of specific role of permanent hyperventilation in ventricle remodeling and mandatory systematic echocardiological control of these patients.

Relating the number of human leucocytes antigen mismatches to pregnancy complications in oocyte donation pregnancies: study protocol for a prospective multicentre cohort study (DONOR study).

IntroductionOocyte donation (OD) enables women with reproductive failure to conceive. Compared with naturally conceived (NC) and in vitrofertilisation (IVF) pregnancies, OD pregnancies are associated with a higher risk of pregnancy complications. The allogeneic nature of the fetus in OD pregnancies possibly plays a role in the development of these complications. The objective of the current study is therefore to study the number and nature of human leucocyte antigen (HLA) mismatches between fetus and mother and its association with the development of hypertensive pregnancy complications.Methods and analysisIn this prospective multicentre cohort study, 200 patients visiting one of the 11 participating fertility centres in the Netherlands to perform OD or embryo donation or surrogacy will be invited to participate. These patients will be included as the exposed group. In addition, 146 patients with a NC pregnancy and 146 patients who applied for non-donor IVF are included as non-exposed subjects. These groups are frequency matched on age and ethnicity and only singleton pregnancies will be included. The primary clinical outcome of the study is the development of hypertensive disease during pregnancy. Secondary outcomes are the severity of the pre-eclampsia, time to development of pre-eclampsia and development of other pregnancy complications. The association of high number of HLA mismatches (>5) between mother and fetus will be determined and related to clinical outcome and pregnancy complication.Ethics and disseminationThis study received ethical approval from the medical ethics committee in the Leiden University Medical Centre, the Netherlands (P16.048, ABR NL56308.058.16). Study findings will be presented at (inter) national conferences and published in peer-reviewed journals.

Genetics and pathophysiology of low-renin arterial hypertension

The review is devoted to the consideration of genetic determination and pathophysiology of one of the forms of hypertensive disease known as low-renin hypertension. At frst glance, the development of low-renin hypertension is “unnatural”, as renin, as a key enzyme of the renin-angiotensin system, which plays an important role in the development of hypertensive disease, is suppressed in low-renin hypertension. At the same time, the most important drugs actual in the treatment of hypertensive disease belong to the renin-angiotensin system blockers. This contradiction was resolved by a study of genetic and pathophysiological mechanisms of hypertension in some groups of patients with characteristic symptoms bringing these people together. Genetic studies of some recent decades using both family analysis and modern molecular genetic technologies have revealed the main mechanisms underlying low-renin hypertension, which can be classifed as certain syndromes with well-defned genetic and clinical features. These syndromes include cases of sporadically occurring somatic mutations in the cells of the adrenal cortex, which begin to produce aldosterone in increased amounts. Also, several oligogenic forms of low-renin hypertension were studied, some of which are associated with the hyperproduction of aldosterone, but in the others the development of low-renin hypertension was associated with mutations of genes involved in regulation of the functioning of the kidney ion channels. The discovery of some types of arterial hypertension with known mechanisms of their development is of paramount importance for medicine, as it allows for targeted efective therapy and in some cases for achieving a complete cure. However, the main contingent of patients with low-renin hypertension belongs to cases with unexplained etiology, as their development is associated with polygenic systems and with a signifcant influence of numerous environmental factors. The study of genetic and physiological mechanisms of various forms of low-renin arterial hypertension provides a good example of how penetration into the intimate mechanisms of the blood pressure regulation in each personal case makes it possible to identify some specifc syndromes and establish its fnal causes. It seems that progress in understanding the causes and mechanisms of essential hypertension lies along this way.

A15069 Nanocomposite (Si-ODN-II), containing antisense oligonucleotides targeted to mRNA of the beta-1-adrenoreceptors for hypertension therapy in rats with stress-sensitive arterial hypertension (ISIAH rats)

Objectives: The study of the possibility of gene therapy of hypertensive disease using nanocomposite (Si-ODN-II), containing silicon and antisense oligonucleotides directed to mRNA of the beta 1-adrenoreceptors in rats with stress-sensitive hypertension (ISIAH rats). Methods: We used the ISIAH rats, hypertension of which was the result of a severe hereditary predisposition to the development of hypertensive state provoked by emotional stress. PCR real-time revealed enhanced mRNA of Adrb1 receptors in myocardium of the intact ISIAH rats. The inhibition of expression Adrb1 gene was studied using intravenous administration of the Si∼ODN-II antisense nanocomposites. Results: Stimulations of the beta 1-adrenoreceptors cause an increase in the frequency and strength of the heartbeats and are one of the factors in the development of hypertensive disease. Beta-blockers help to slow down the heart rhythm and lower the blood pressure. At the first stage of the work, high expression of the mRNA of the Adrb1 gene in the myocardium in intact ISIAH rats was observed. Further, we investigate the action of the Si ∼ODN-II nanocomposite with antisense ODN to the mRNA of Adrb1 gene on arterial pressure using intravenous administration. Intravenous injection of Si∼ODNI nanocomposite into the ISIAH rats led to a drop in blood pressure of 10–12 mm Hg for four to five days. Conclusion: The study revealed high expression of mRNA Adrb1 in the myocardium of ISIAH rats. Using of Si∼ODN-II nanoparticles with antisense ODN to beta 1-adrenergic receptors by intravenous administration led to a prolonged decrease in arterial pressure in the ISIAH rats, which is an advantage over traditional drugs and has an perspective to be used in clinical practice. The work was supported by the Russian Science Foundation, grant 16–15-10073.

Stress and arterial hypertension: ISIAH rat strain

The main views of the issue of stress and hypertension are briefly reviewed. It is well known that stress is one of the major risk factors for cardiovascular disease development. Increase in blood pressure is a typical manifestation of the acute stress response. This fact is the reason to hypothesize that chronic stress causes the development of hypertensive disease. An association of hypertension with psychological stress in humans was shown in several works. In addition, it was demonstrated that hypertension was accompanied by an increase in sympathetic tone. On the other hand, there were many population studies in which no association was found between different types of chronic stress and arterial hyper­tension. Thus, the question is far from being answered. Even in the cases when one managed to obtain a signi­ficant hypertensive effect in experimental studies with emotional stress, it was difficult to explain the mechanisms mediating the formation of stressinduced hypertension. To clarify the situation, one of the authors of this review decided to begin the breeding of a rat strain with increased blood pressure response to emotional stress. This breeding gave rise to inbred rats with persistent stress-induced arterial hypertension. A brief history of the development of the genetic model ofstress-induced arterial hypertension, the ISIAH rat strain, is given. A retrospective review of the studies performed with ISIAH rats is presented. The contribution of genotype changes in the neuroendocrine systems involved in stress and blood pressure regulation to the development ofstress-dependent hypertension in the ISIAH rat strain is shown.

Evolutionary and genetic roots of hypertensive disease

This review concerns issues related to the evolutionary and genetic origins of hypertensive disease. An evolutionary approach is used to account for the predisposition of modern people to the development of a pathology such as hypertensive disease. Many studies indicate the importance of "ancestral" alleles, which provided perfect adaptation to the environment and lifestyle of our distant relatives, with respect to the increase in hypertensive disease development among modern individuals.

Doppler Tissue Imaging Is More Sensitive Than Other Echocardiographic Markers in Identifying Abnormal Relaxation in Subclinical Hypertensive Disease and Normal Ejection Fraction

This report describes the use of echocardiographic measurements for the assessment of left ventricular diastolic function in two young patients with newly diagnosed hypertension. Measurements for the assessment of left ventricular relaxation and filling pressures included mitral inflow, Doppler tissue imaging (DTI), color M-mode propagation velocity slope, and the isovolumic relaxation time. The mitral inflow, propagation velocity, and isovolumic relaxation time measurements were all within normal limits; however, DTI measurements of the E′ velocity at the septal and lateral annulus were significantly reduced in both patients. Further visual inspection demonstrated discrete proximal septal wall thickening that is thought to be modulated by pressure loading (i.e., increased afterload due to hypertension) and ejection. These findings may represent a “transitional state” of early ventricular remodeling and organ failure in the development of hypertensive disease. In summary, DTI appears to be more sensitive compared to other markers in identifying abnormal relaxation in subclinical hypertensive disease and normal ejection fraction.

Modeling of the Blood Pressure Regulation System in Rats Using Genetic Algorithms

Abstract Blood pressure (BP) is one of the principal vital signs. The regulation of normal BP is critical for maintaining the normal functioning of an organism. The structure of the BP regulation in vertebrates, including humans, is very complex and it is not yet fully understood. There are several BP regulation subsystems which interact together. In this study, we analysed and modelled the role of the most important BP regulation systems (sympathetic nervous system, renin-angiotensin-aldosterone system, L-Arginine/nitric oxide) as well as the role of reactive oxygen species, the imbalance of which is implied in the development of hypertension disease. Our aim is to design a dynamic model of the BP regulation in normotensive rats, which can help us better understand the complex process of BP regulation. The BP responses were measured in conscious rats after acute stress with or without the application of selected drugs, which can inhibit particular regulation subsystems. Linear dynamic models of particular regulation subsystems were identified using genetic algorithms. Each subsystem is a feedback loop, which contains both the system dynamics and the controller. We describe the simulation-based identification procedure of these particular models as well as of the entire BP regulation system.

Pre-eclampsia and gestational hypertension are less common in HIV infected women.

To determine whether pre-eclampsia and gestational hypertension are less common in HIV infected women. This prospective cohort study was performed in the Western Cape province of South Africa. HIV negative and positive pregnant women without chronic renal or chronic hypertensive disease were continuously recruited. During the study period HIV positive patients received either mono- or triple (HAART) antiretroviral therapy for prevention of vertical transmission or maternal care. Only routine clinical management was performed. The development of hypertensive disease during pregnancy was recorded. 1093 HIV positive and 1173 HIV negative cases were identified during pregnancy and evaluated again after delivery. Significantly fewer cases of pre-eclampsia n=35 (3.2%) were recorded in the HIV positive group than in the HIV negative group, n=57 (4.9%) (p=0.045; OR 0.65 95% CI 0.42-0.99). There were also significantly fewer cases of gestational hypertension recorded in the HIV positive group compared to the HIV negative group (p=0.026; OR 0.53 95% CI 0.30-0.94). Multiple logistic regression analysis confirmed the reductive effect of HIV on pre-eclampsia and gestational hypertension. Pre-eclampsia and gestational hypertension are less common in HIV infected women being managed with mono- or triple anti-retroviral therapy.

Blood pressure homeostasis is maintained by a P311–TGF-β axis

P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311-/- mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice resulted from decreased total and active levels of TGF-β1, TGF-β2, and TGF-β3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-β1-TGF-β3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-β1-TGF-β3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-β translation and the first pan-regulator of TGF-β expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease.

The renin–angiotensin system is modulated by swimming training depending on the age of spontaneously hypertensive rats

AimTo investigate the effects of swimming training on the renin–angiotensin system (RAS) during the development of hypertensive disease. Main methodsMale spontaneously hypertensive rats (SHR) were randomized into: sedentary young (SY), trained young (TY), sedentary adult (SA), and trained adult (TA) groups. Swimming was performed 5 times/wk/8wks. Key findingsTrained young and adult rats showed both decreased systolic and mean blood pressure, and bradycardia after the training protocol. The left ventricular hypertrophy (LVH) was observed only in the TA group (12.7%), but there was no increase on the collagen volume fraction. Regarding the components of the RAS, TY showed lower activity and gene expression of angiotensinogen (AGT) compared to SY. The TA group showed lower activity of circulatory RAS components, such as decreased serum ACE activity and plasma renin activity compared to SA. However, depending on the age, although there were marked differences in the modulation of the RAS by training, both trained groups showed a reduction in circulating angiotensin II levels which may explain the lower blood pressure in both groups after swimming training. SignificanceSwimming training regulates the RAS differently in adult and young SHR rats. Decreased local cardiac RAS may have prevented the LVH exercise-induced in the TY group. Both groups decreased serum angiotensin II content, which may, at least in part, contribute to the lowering blood pressure effect of exercise training.

INVEST substudies: design and patient characteristics.

The INternational VErapamil SR/trandolapril STudy (INVEST) will provide a large database of information. Proposed substudies for analysis include ambulatory blood pressure monitoring (ABPM), depression, genotyping, atrial fibrillation, electrocardiogram (ECG), echocardiography, renal dysfunction, diabetes, and cardiac care cost estimate. This paper reviews the design and status of several of the INVEST substudies. The ABPM substudy will obtain objective blood pressure recordings during daily life masked to both the patient and the investigator. Ambulatory blood pressure monitoring is an especially useful technology because of the role of nocturnal hypertension and circadian blood pressure irregularities in the development of hypertensive disease. The depression substudy, which enrolled 2,393 patients in the United States, will report quality-of-life (QOL) data, including information regarding energy and fatigue. The genotyping substudy will provide genomic DNA samples from approximately 15,000 patients in the United States, including Puerto Rico. Many candidate genes will be examined for polymorphisms that may predict outcomes and/or responses to various treatments.

Evaluating the Role of Bedrest on the Prevention of Hypertensive Diseases of Pregnancy and Growth Restriction

Background. Evaluating the effect of restricted activity on the development of preeclampsia under experimental clinical settings has been compromised by inherent selection bias and differential misclassification. The aim of our study was to overcome such limitations by using hospitalized bedrest for preterm labor/birth-related indications as an unbiased measure of restricted activity and evaluate its effect on the development of hypertensive diseases of pregnancy. Methods. We conducted a retrospective cohort study using data from the McGill Obstetrical and Neonatal Database on all pregnancies that took place between 1991 and 2001. We defined “exposure” as hospitalized bed rest for preterm labor/birth related indications and used unconditional logistic regression models to estimate its adjusted effect on the development of hypertensive diseases of pregnancy. Results. Data were available on 36,140 pregnancies. 677 women were hospitalized and prescribed bedrest for either preterm contractions (71%), preterm premature rupture of membranes (18%), an incompetent cervix (8%), or other indications. Among all women, bedrest was associated with a significant reduced risk for developing preeclampsia, 0.27 (0.16–0.48). In a stratified analysis, women delivering prior to 34 weeks of gestation had an even more pronounced reduced risk for developing preeclampsia 0.12 (0.03–0.50) as well as a reduced risk for developing intrauterine growth restriction 0.38 (0.18–0.84). Conclusion. When strictly adhered to, bedrest may be an effective measure in the prevention of preeclampsia and early intrauterine growth restriction.

The significance of under- or overweight during childhood as a risk factor for hypertensive diseases in pregnancy

Hypertensive diseases in pregnancy are still a major cause of foetal and maternal mortality. Known risk factors allow identification of only a small number of patients at risk of developing such a complication. However, better knowledge of the risk profile would improve an early adequate monitoring of these pregnancies. We therefore investigated the correlation between under- or overweight during childhood and the development of hypertensive diseases during pregnancy. The study was designed as a cross-sectional case control study. A self-administered questionnaire was distributed to 2600 women, who had contacted the German pre-eclampsia self-help group for information on hypertensive diseases in pregnancy and 1233 control women recruited in different hospitals. Diagnosis according to criteria of the international society for hypertensive diseases in pregnancy was based on medical records. 766 women with a hypertensive disease during their pregnancy and 951 control women with normal pregnancies were evaluated after verifying for exclusion criteria and complete data sets. Student t-test, chi square test and multivariate logistic regression models were used for statistical analysis. A history of under- (OR 2.1, 95% CI 1.23–3.61) or overweight (OR 1.46, 95% CI 1.01–2.12) during childhood is associated with an increased risk for hypertensive diseases in pregnancy, which is at least partly independent of pre-pregnancy BMI. In combination with other risk factors, a history of under- or overweight during childhood will help to identify patients at risk for hypertensive diseases in pregnancy.

Family stability during childhood and the risk to develop hypertensive diseases in pregnancy

Background Parental care giving, divorce and death are associated with physical health as an adult. Aim To investigate whether the structure of the nuclear family during childhood shows any correlation with the development of hypertensive diseases in pregnancy as an adult. Study design Self-administered questionnaires were sent to 2600 women with hypertensive diseases in pregnancy and to 1484 controls. Subjects After confirmation of the diagnosis data from 842 patients and 623 control women were evaluated. Outcome measures Type, number and involvement of different caregivers, parental separation, parental death. Results In both groups parental separation and parental death were found equally often. In all age groups during childhood fathers were involved significantly less often in care giving when women with hypertensive disorders in pregnancy were compared to control women (1st–3rd year 23.4% / 17%, < 0.0001; 4th–10th year 25.7% / 19.3%, < 0.0001; 11th–18th year 30.1% / 23.9%, < 0.0001). The total number of caregivers involved was significantly higher in patients. Conclusions The quality of parental care giving, i.e. the involvement of fathers and the total number of caregivers correlate with the risk to develop HDP. Further research is needed to specify underlying mechanisms and the relevant factors of the parent–child relationship.

Cardiovascular implications of anabolic steroid abuse

Anabolic steroids are synthetic derivatives of the hormone testosterone. Anabolic effects such as anticatabolism, increased skeletal muscle mass, and increased aggressiveness are usually desired; however, androgenic effects also result. Decreases in high-density lipoprotein, increases in low-density lipoprotein, changes in total serum cholesterol, hematocrit, and clotting factors, and the development of hypertensive diseases have all been implicated as resulting from anabolic steroid use. Research does not directly link anabolic steroids with cardiovascular diseases, but steroid use can significantly increase risk factors for atherosclerotic cardiovascular disease.

Cardiovascular implications of anabolic steroid abuse

Anabolic steroids are synthetic derivatives of the hormone testosterone. Anabolic effects such as anticatabolism, increased skeletal muscle mass, and increased aggressiveness are usually desired; however, androgenic effects also result. Decreases in high-density lipoprotein, increases in low-density lipoprotein, changes in total serum cholesterol, hematocrit, and clotting factors, and the development of hypertensive diseases have all been implicated as resulting from anabolic steroid use. Research does not directly link anabolic steroids with cardiovascular diseases, but steroid use can significantly increase risk factors for atherosclerotic cardiovascular disease.

Structural adaptation in borderline hypertension.

Animal studies have shown that the cardiovascular system adapts to blood pressure elevation very early in the development of hypertensive disease. This discussion is concerned with structural adaptation in mild or borderline hypertension in humans. A literature review is given, followed by some preliminary data from a current hemodynamic follow-up study on young individuals with mild blood pressure elevation. Hand blood flow at maximal vasodilatation was studied plethysmographically, the baroreceptor reactivity was investigated by analyzing heart rate after intravenously administered angiotensin, and the left ventricle wall thickness was evaluated with M-mode echocardiography. The results indicate that the resistance vessels, the high-pressure baroreceptors, and the left ventricle of the heart are structurally modified even in very mild blood pressure elevation.