Determinants Of Blood Pressure Research Articles

Socioeconomic Position, But Not African Genomic Ancestry, Is Associated With Blood Pressure in the Bambui-Epigen (Brazil) Cohort Study of Aging.

The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use. We used 370 539 single-nucleotide polymorphisms to estimate each individual's African, European, and Native American trihybrid ancestry proportions. Median African, European, and Native American ancestry were 9.6%, 84.0%, and 5.3%, respectively. Among those with African ancestry, 59.4% came from East and 40.6% from West Africa. Baseline systolic and diastolic blood pressure, controlled hypertension, and their respective trajectories, were not significantly (P>0.05) associated with level (in quintiles) of African genomic ancestry. Similar results were found for West and East African subcontinental origins. Lower schooling level (<4 years versus higher) showed a significant and positive association with systolic blood pressure (Adjusted β=2.92; 95% confidence interval, 0.85-4.99). Lower monthly household income per capita (<USD 180.00 versus higher) showed an inverse association with hypertension control (β=-0.35; 95% confidence interval, -0.63 to -0.08, respectively). Our results support the view that favors social and environmental factors as determinants of blood pressure and hypertension control.

Body Weight and Not Exercise Capacity Determines Central Systolic Blood Pressure, a Surrogate for Arterial Stiffness, in Children and Adolescents.

Cardiopulmonary fitness benefits cardiovascular health. Various studies have shown a strong negative correlation between exercise capacity and arterial stiffness in adults. However, evidence for this connection in children and adolescents is scarce. About 320 healthy children and adolescents (252 male, 14.0±2.1 years) were evaluated with regard to their demographic, anthropometric and hemodynamic parameters, and their peak oxygen uptake. Peripheral and central systolic blood pressures were measured with patients in a supine position using an oscillometric device. Peak oxygen uptake was assessed by cardiopulmonary exercise testing. In multivariate regression, only peripheral systolic blood pressure (β=0.653, P<.001) and body weight (β=0.284, P<.001) emerged as independent determinants for central systolic blood pressure. Body weight therefore determines central systolic blood pressure in children and adolescents rather than measures of cardiorespiratory fitness. The prevention of overweight in childhood is necessary to reduce stiffening of the arteries and delay the onset of cardiovascular disease.

Blood pressure in the Congolese adult population of South Kivu, Democratic Republic of Congo: Preliminary results from the Bukavu Observ Cohort Study

BackgroundProviding factual data about non-communicable diseases (NCDs) is of utmost importance in the sub-Saharan African countries where NCDs and arterial hypertension data remain scattered, scarce, and less representative given the region's heterogeneous population. Within this context, the interuniversity cooperation VLIR-UOS/Catholic University of Bukavu (Democratic Republic of Congo) has established an integrated project for monitoring hypertension and cardiovascular risk factors in the population of South Kivu. The aim of the study was to present the basic results of the determinants of blood pressure in the cohort studied. MethodsIn 2013 and 2014, trained interviewers collected the anthropometric parameters, blood pressure, and medical history of 7405 adults (3060 in urban areas and 4345 in rural areas) including 3162 males and 4243 females; the cohort is expected to be followed for 9 years. ResultsThe average age of the entire group was 33.0±16.7 years. Compared to men, women had significantly higher obesity indices (P<0.0001), lower blood pressure between 20 and 39 years of age (P<0.0001) but higher blood pressure at 60 years of age and older (P<0.0001). Blood pressure was positively correlated with body mass index, waist circumference, and paradoxically with consumption of vegetables, but negatively correlated with the consumption of fruit, intense physical activity, and relaxation at home. ConclusionsThese results show that a cohort study is feasible in the Democratic Republic of Congo. The factual data analysis can contribute to health policy orientation and setting up of preventive measures. Since most correlated risk factors are preventable, recommendations can already be made in the fight against high blood pressure in this population.

Resistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity.

The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognized as a chronic, low level inflammatory condition, and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well-known adipokine released from fat tissue is leptin. The adipokine, resistin, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other's actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity.

A Western dietary pattern is associated with higher blood pressure in Iranian adolescents.

The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents. This cross-sectional study was conducted among a representative sample (n=557) of Shirazi adolescents aged 12-19years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups. Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9mmHg, P=0.001; and for mean BP: mean difference 4.2mmHg, P=0.003). A similar but statistically insignificant difference was observed in terms of diastolic BP. The findings suggest that a Western dietary pattern is associated with higher BP in Iranian adolescents. However, additional large-scale prospective studies with adequate methodological quality are required to confirm these findings.

Balancing Sodium and Potassium: Estimates of Intake in a New Zealand Adult Population Sample.

Dietary intakes of sodium and potassium are important determinants of blood pressure. We assessed sodium and potassium intake in a cross-sectional survey which included a random sample of New Zealand Adults aged 18 to 64 years from two New Zealand cities: Dunedin and Wellington. Participants completed a short questionnaire, had height, weight and blood pressure measured, and collected a 24 h urine sample. Mean 24 h sodium excretion was 3386 mg/day (95% CI 3221, 3551): 3865 mg/day for men and for 2934 mg/day women. Mean 24 h potassium excretion was 2738 mg/day (95% CI 2623, 2855): 3031 mg/day for men and 2436 mg/day for women. Mean sodium:potassium ratio was 1.32 (95% CI 1.26, 1.39); 1.39 for men and 1.26 for women. Sodium intake was higher among younger people, men, those with a higher BMI and higher potassium excretion. Potassium excretion was higher among older people, men and those with a higher sodium excretion. New Zealand adults have high sodium intakes and low potassium intakes compared to recommended levels. This is likely to adversely affect population blood pressure levels as well as incidence of cardiovascular disease. A comprehensive public health programme to reduce dietary sodium intake and increase intake of fruit and vegetables is warranted.

Hyperuricemia induces hypertension through activation of renal epithelial sodium channel (ENaC)

ObjectivesThe mechanisms leading to hypertension associated with hyperuricemia are still unclear. The activity of the distal nephron epithelial sodium channel (ENaC) is an important determinant of sodium balance and blood pressure. Our aim was to investigate whether the effect of hyperuricemia on blood pressure is related to ENaC activation. MethodsA hyperuricemic model was induced in rats by 2% oxonic acid and 6mg/dl uric acid (UA). The hyperuricemic rats were co-treated with either 10mg/kg/d benzbromarone (Ben) or 1mg/kg/d amiloride (Ami). Blood pressure was monitored using a tail-cuff, and blood, urine, and kidney samples were taken. Western blotting and immunohistochemical staining were performed to determine the expressions of ENaC subunits and components of the ENaC Regulatory Complex (ERC) in kidney tissue or mCCD cells. ResultsSerum uric acid (SUA) was increased 2.5–3.5 times above normal in hyperuricemic rats after 3weeks and remained at these high levels until 6weeks. The in vivo rise in SUA was followed by elevated blood pressure, renal tubulointerstitial injury, and increased expressions of ENaC subunits, SGK1, and GILZ1, which were prevented by Ben treatment. The decrease in urinary Na+ excretion in hyperuricemic rats was blunted by Ami. UA induced the expression of all three ENaC subunits, SGK1, and GILZ1, and increased Na+ transport in mCCD cells. Phosphorylation of ERK was significantly decreased in both UA-treated mCCD cells and hyperuricemic rat kidney; this effect was prevented by Ben co-treatment. ConclusionOur findings suggest that elevated serum uric acid could induce hypertension by activation of ENaC and regulation of ERC expression.

Longitudinal Assessment of Blood Pressure in School-Aged Children: A 3-Year Follow-Up Study.

The purpose of this study was to assess the prevalence of abnormal blood pressure in a population of school children during a 3-year follow-up period and its relationship with obesity. Anthropometric and blood pressure data were collected from a population of Italian school children during three consecutive years. During each year blood pressure measurements were repeated three times, at intervals of 1 week. A total of 564 school-children [311 boys; mean (SD) age 8.8 ± 1.4 years] were recruited. During each year, systolic and diastolic blood pressure decreased from visit 1 to visit 3 (p < 0.001). This was associated with a decline in the percentage of prehypertension/hypertension from visit 1 to visit 3. An abnormal blood pressure value in at least one study visit was found in 8.8-17 % of children, whereas the prevalence of hypertension at all three study visits was between 5.2 and 7.8 %, and that of prehypertension at all three visits was between 2.8 and 3.8 %. High blood pressure was more frequent in obese children. In this population of school children the percentage of prehypertension/hypertension remarkably varied when based on one versus three annual assessments, thus emphasizing the importance of repeated measurement before making a diagnosis of abnormal blood pressure. Adiposity was confirmed to be a determinant of high blood pressure.

Abstract 043: A Gwas Prioritized Candidate Gene,Nr2f2, Attenuates Salt-sensitive Hypertension and Associated Renal Function

A haplotype-based re-analysis of the GWAS study by the Wellcome Trust Case Control consortium prioritized the transcription factor, Nuclear receptor2, family2 (NR2F2) also known as Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) as a gene associated with essential hypertension in humans. This gene is also prioritized as a differentially expressed positional BP QTL candidate gene on rat chromosome 1. To further examine Nr2f2 as a determinant of blood pressure, a mutant Dahl salt-sensitive (S) rat model was generated using the zinc-finger nuclease (ZFN) technology. As a result of this ZFN mediated disruption, a 15-bp deletion occurred within exon 2 of the Nr2f2 locus, resulting in the loss of 5 amino acids from the hinge region of the Nr2f2 protein. Systolic BP of the homozygous Nr2f2mutant rats was lower than that of the S rats (179±3 vs. 197±5 mmHg; p&lt;0.001) as measured by the tail-cuff method and (165±2 vs. 201±3 mmHg; p&lt;0.001) as monitored by the radio-telemetry method. Nr2f2mutant rats demonstrated lower proteinuria compared to S rats (87.97±7.07 vs. 122.63±7.07mg/day; p&lt;0.05). Since Nr2f2 is reported to negatively regulate renin promoter activity, we tested renin activity in the Nr2f2mutant rats. However, there was no significant difference in either the plasma renin activity or renal renin protein expression when compared with S rats. Renal histological analysis showed that Nr2f2mutant rats have decreased collagen compared with the S rats. Furthermore, Nr2f2mutant rats showed significantly decreased TGF-β protein levels, when compared with S rat kidney (p&lt;0.05). These data, taken together with our recently published data on the improved cardiac and vascular function in the Nr2f2mutant rats (Nat Commun. 2015 Feb 17;6:6252), lend support to Nr2f2 as a determinant of blood pressure and associated renal function. While the observed improvement in renal function could be a secondary consequence of lower hypertension, our data, combined with the important mechanistic finding that the enhanced transcription factor-transcription factor interaction of Nr2f2 with Fog2 (Friend of GATA4), suggest that the hinge region of Nr2f2 is important for regulating blood pressure and associated cardiac and renal functions.

Hypertension Control and Its Correlates Among Adults Attending a Hypertension Clinic in Tanzania.

Hypertension control rates are low in sub-Saharan Africa. Population-specific determinants of blood pressure (BP) control have not been adequately described. The authors measured BP and conducted interviews to determine factors associated with BP control among adults attending a hypertension clinic in Tanzania. Three hundred adults were enrolled. BP was controlled in 47.7% of patients at the study visit but only 28.3% over three consecutive visits. Demographic and socioeconomic factors were not associated with control. Obesity and higher medication cost were associated with decreased control. Their effect was mediated through adherence. Good knowledge of (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0-6.1; P=.047), attitudes towards (OR, 2.7; 95% CI, 1.0-7.1; P=.04), and practices concerning (OR, 5.4; 95% CI, 2.3-13.0; P<.001) hypertension were independently associated with increased control, even after adjusting for mediation through adherence. Good adherence had the strongest association with control (OR, 14.6; 95% CI, 5.8-37.0; P<.001). Strategies to reduce hypertension-related morbidity and mortality in sub-Saharan Africa should target these factors. Interventional studies of such strategies are needed.

Sex differences and blood pressure regulation in humans.

What is the topic of this review? Over the past decade, our team has investigated interindividual variability in human blood pressure regulation. What advances does it highlight? In men, we have found a tight relationship between indices of sympathetic activity and vascular resistance across the age span. This relationship is absent in young women but seen in postmenopausal women. These sex and age differences in vascular resistance are largely a result of changes in the balance of vasodilating and vasoconstricting adrenergic receptor tone. When these changes are considered along with cardiac output, a coherent picture is beginning to emerge of why blood pressure rises more with age in women than men. Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12 years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because β-adrenergic vasodilator mechanisms offset α-adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, β-adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age-related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups.

PlGF, immune system and hypertension

The huge diffusion of hypertension and its associated complications has a significant impact on public health [1]. However, despite the high prevalence of essential hypertension and many efforts of research, the basic pathophysiological causes remain puzzling. Although in the simplest way, the determinants of blood pressure (BP) are approximated by physical laws for fluid dynamics, these components of BP and their interactions have been intensely examined for years, without untangling the core of the problem. A more recent field of studies in hypertension has begun to shed light on a previously unpredictable role of the immune system in regulating BP [2]. Nevertheless, even though it is now recognized that T cell response drives hypertension, the key immune pathways contributing to BP elevation are still unidentified. Our recent work outlined an unprecedented role of immune system in the spleen, orchestrating the response of T cell to hypertensive challenge, through the angiogenic factor named Placental Growth Factor (PlGF) [3]. Two main points emerge in our study. First, the finding that PlGF-deficient mice manifest protection from AngII-induced hypertension, one of the most common experimental models of hypertension. Second, our work highlighted an unprecedented and unexpected role of the splenic neuroimmune interaction in hypertension. Although the fact that T cells are recruited in the vasculature during hypertension has been well documented, how and where they are activated was still unclear. In our paper, we have defined that the spleen is crucial in the onset of hypertension, given that splenectomized mice are protected from the blood pressure raising typically occurring upon chronic infusion of AngII. Moreover, the sympathetic drive converging in the spleen and departing from the celiac ganglion is necessary for the induction of PlGF in the MZ of splenic reservoir upon the AngII hypertensive challenge. Thus, we started to think about a “neuroimmune” pathway mediated by PlGF and necessary for the onset of hypertension. The generation of chimeric mice, obtained by spleen transplantation and harboring a PlGF-deficient spleen in a WT background and the contrary, allowed us to finally demonstrate that PlGF is needed in the spleen to allow the activation of T cells and blood pressure raising. Once activated in the spleen, PlGF is crucial to allow T cell costimulation via CD86 and their consequent egress for the deployment toward vasculature of target organs, a hallmark of hypertension. The identification of an epigenetic modulation, responsible for the PlGF-mediated mechanism of T cells costimulation, highlights intriguing questions that range over cardiology toward oncology. In particular, we found that the co-stimulatory molecule CD86 is regulated by Timp3 expression, depending in turn on the activity of Sirt1 deacetylase activity on p53 repressor activity. Despite the unquestionable basic research implications that our results would have in the evergrowing field of studies on immune system and hypertension, what is more important is the opportunity arousing in terms of therapeutic potential. Indeed, the possibility to use potent immunosuppressive agents to treat uncomplicated hypertension would inevitably provoke some uncertainty. On the other hand, with the identification of key immune pathways contributing to BP elevation, specific therapeutic interventions might be devised to ameliorate hypertension, minimizing the potential immunosuppressive deleterious effects. On this issue, PlGF appears as an appealing molecular target for therapeutic implications, since tools clinically affording this pathway already exist [4, 5]. In the last years, anti-PlGF monoclonal antibodies have been developed as a strategy to slow tumor growth and for age-related macular degeneration. The ongoing clinical trials, testing humanized monoclonal antibodies directed to PlGF, encourage the possibility to endeavor this way also in hypertension and hopefully fulfill the pressing priority to reach satisfactory control rates in the substantial proportion of people with hypertension that, although under treatment, do not achieve the BP target levels recommended by current guideline. At same time, our findings encourage a reflection about the possibility that some of the effects so far attributed to PlGF inhibition in cancer may rely on the previously unknown capability to exert an epigenetic modulation of p53-Timp3 axis, which is well known to play a crucial role also in tumor growth. Further studies directed at this issue, could help to explain how a single molecule like PlGF could play so wide and, at same time similar, effects in different pathophysiological context, like hypertension and cancer.

Resting Plasma Lipids and Cardiovascular Reactivity to Acute Psychological Stress

Abstract. Prior research suggests that hyperlipidemia is associated with elevated blood pressure responses to acute stress but whether lipid levels influence underlying cardiac and vascular determinants of blood pressure during stress is not known. Thus, we examined whether lipids were associated with stress-induced blood pressure responses and responses of stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR). In 19 healthy university students (15 men), blood was drawn to measure lipid levels (triglycerides, low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], total cholesterol) after a 10-min rest period. Participants then completed a 6-min mental arithmetic stressor and a 3-min cold pressor (separated by a 10-min recovery). This procedure was repeated twice, approximately 6 weeks apart. Lipids and hemodynamic values were averaged across the two sessions. Multiple linear regression analyses revealed that a model including LDL-c, HDL-c, and triglycerides significantly predicted diastolic blood pressure (DBP), R2adj = .45, p = .007, and systolic blood pressure (SBP) cold pressor reactivity, R2adj = .35, p = .023. Individually, only LDL-c significantly predicted DBP, β = .64, p = .003, and SBP cold pressor reactivity, β = .64, p = .005. The same model marginally predicted CO, R2adj = .24, p = .069, and TPR, R2adj = 21, p = .091, reactivity to mental arithmetic, but only triglycerides were independently associated with CO, β = −.63, p = .012, and TPR, β = .54, p = .029 reactivity. Lipids were not associated with heart rate (HR) or SV reactivity. LDL-c was positively associated with the blood pressure response to the cold pressor, whereas triglycerides were positively and negatively associated with the TPR and CO responses, respectively, to mental arithmetic. Endothelial dysfunction and greater release of vasoconstrictors in those with high lipids may explain these relationships.

G-protein-mediated signaling in vascular smooth muscle cells — implications for vascular disease

Differentiated vascular smooth muscle cells (VSMCs) are critical determinants of vascular tone and blood pressure. However, during vascular remodeling processes, which occur in response to changing hemodynamics or vascular injury, VSMCs lose most of their contractile functions in a dedifferentiation process, which goes along with cell proliferation and cell migration. VSMCs are under the constant control of a variety of mediators with vasocontractile or vasodilatory properties. Most of these mediators act through G-protein-coupled receptors, which, via different downstream signaling pathways, regulate the phosphorylation of myosin light chain and thereby control vascular tone. Recent work indicates that procontractile G-protein-mediated signal transduction pathways are also critical regulators of vascular smooth muscle dedifferentiation and redifferentiation. This review describes some of the key G-protein-mediated signal transduction pathways regulating vascular tone and VSMC differentiation and their involvement in cardiovascular diseases.

Epicatechin induced vasorelaxation of human internal mammary artery

Epicatechin induced vasorelaxation of human internal mammary artery

Relations between retinal arterioles anatomy and large artery geomtry and function and peripheral resistance in hypertensives

Background: Microvascular remodeling and large artery stiffness are key determinants of blood pressure (BP) yet they are difficult to study non-invasively in humans. Our objective was to study relationships between retinal arterioles anatomy and total peripheral resistance (TPR) as well as with large artery geometry and function in hypertension.

5 Major Adverse Cardiovascular Events at 30-days were not Significantly different between Frail and non-frail older (≥75 years) Patients with non ST Elevation Acute Coronary Syndrome Managed by Invasive Strategy: An Analysis from the ICON1 Study: Abstract 5 Table 1

OBJECTIVE--To evaluate the relative contributions of factors acting at different stages in life to regional differences in adult blood pressure. DESIGN--Prospective cohort study (British regional heart study). SETTING--One general practice in each of 24 towns in Britain. SUBJECTS--7735 Men aged 40-59 years when screened in 1978-80 whose geographic zone of birth and zone of examination were classified as south of England, midlands and Wales, north of England, and Scotland. Non-migrants (n = 3144) were born in the town where they were examined; internal migrants (n = 4147) were born in Great Britain but not in the town where they were examined; and international migrants (n = 422) were born outside Great Britain. MAIN OUTCOME MEASURES--Systolic and diastolic blood pressures and height. RESULTS--Regardless of where they were born, men living in the south of England had lower mean blood pressures than men living in Scotland (142.5/80.1 v 148.1/85.2 mm Hg). The effects of the place of birth and place of examination on adult blood pressure were examined in a multiple regression model. For internal migrants the modelled increase in mean systolic blood pressure across adjacent zones of examination was 2.1 mm Hg (95% confidence interval 1.3 to 2.9); for adjacent zones of birth the corresponding increase was 0.1 mm Hg (-0.7 to 0.7). The place of examination seemed to be a far more important determinant of mean adult blood pressure than the place of birth. Height is an accepted marker of genetic and early life influences. Regional differences in height were therefore analysed to test whether the multiple regression model could correctly distinguish between the influence of place of birth and place of examination. As expected, men born in Scotland were shorter on average than men born in the south of England irrespective of where they lived in Britain (172.6 cm v 175.1 cm for internal migrants). CONCLUSION--Regional variations in blood pressure were strongly influenced by where the men had lived for most of their adult lives rather than by where they were born and brought up. Among middle aged men, factors acting in adult life seemed to be more important determinants of regional differences in blood pressure than those acting early in life such as genetic inheritance, intrauterine environment, and childhood experience.

Hypertension Editors’ Picks

<i>Hypertension</i> Editors’ Picks

Determinants of arterial stiffness and central blood pressure in the very elderly

Pulmonary arterial hypertension (PAH) is a severe and increasingly prevalent disease, manifested by the maladaptation of pulmonary vasculature, which consequently leads to right heart failure and possibly even death. The development of PAH is characterized by specific functional as well as structural changes, primarily associated with the aberrant function of the pulmonary artery endothelial cells, smooth muscle cells, and vascular fibroblasts. MicroRNAs constitute a class of small ≈22–nucleotides–long non–coding RNAs that post–transcriptionally regulate gene expression and that may lead to significant cell proteome changes. While the involvement of miRNAs in the development of various diseases—especially cancer—has been reported, numerous miRNAs have also been associated with PAH onset, progression, or treatment responsiveness. This review focuses on the role of microRNAs in the development of PAH as well as on their potential use as biomarkers and therapeutic tools in both experimental PAH models and in humans. Special attention is given to the roles of miR–21, miR–27a, the miR–17–92 cluster, miR–124, miR–138, the miR–143/145 cluster, miR–150, miR–190, miR–204, miR–206, miR–210, miR–328, and the miR–424/503 cluster, specifically with the objective of providing greater insight into the pervasive roles of miRNAs in the pathogenesis of this deadly condition.

Compromised Salt Dependence of ENaC Activity Upon Deletion of AT1 Receptors

ENaC-mediated sodium reabsorption in the collecting duct (CD) is an essential determinant of blood pressure in humans. Cumulative evidence suggests direct action of Angiotensin II (Ang II) on ENaC activity in the CD, independently of the classical aldosterone signaling. The significance of regulation by Ang II becomes particularly important during Ang II dependent hypertension, when overactive ENaC is poorly regulated via aldosterone – mineralocorticoid receptor (MR) axis. Stimulatory Ang II actions on ENaC are mediated by AT1 receptors (AT1R). AT1R knockouts have decreased blood pressure despite elevated aldosterone levels. This indicates that aldosterone-MR cascade alone cannot provide sufficient input to adequately regulate ENaC-dependent sodium re-uptake. Using freshly isolated split-opened CDs we found that genetic deletion of AT1R markedly diminishes ENaC activity on low and regular sodium intake, significantly blunting salt-dependent regulation of ENaC. The observed decrease of ENaC activity was mainly attributed to a reduced channel open probability (Po). Pharmacological inhibition of AT1R with losartan in wild-type animals reproduces the effect of genetic ablation of AT1R on ENaC activity. Interestingly, saturation of aldosterone signaling with DOCA has minimal stimulatory effect on ENaC upon AT1R deletion, which can be explained by a markedly diminished MR abundance in the CD cells of the knockouts. Overall, genetic ablation of AR1R elicits a complex inhibitory effect on ENaC activity, directly attenuating ENaC Po and precluding adequate compensation by aldosterone cascade due to decreased MR expression.