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Hypertension is an important risk factor for chronic kidney disease and cardiovascular disease. The global prevalence of hypertension is increasing owing to factors including population ageing and obesity. Although hypertension is the most common chronic disease in developing countries, optimal blood pressure control remains challenging and the mechanisms that lead to hypertension and related comorbidities are not fully understood. This series of articles aims to explore basic, clinical and translational aspects of hypertension, including the epidemiology, pathogenesis, patient management and novel therapeutic strategies.
Immune dysregulation contributes to the pathogenesis of preeclampsia. Here, the authors examine the role of immune cells and mediators in driving the oxidative stress and endothelial dysfunction that characterize this hypertensive disorder of pregnancy.
The gut microbiota is increasingly recognized as an important factor in human health and disease. Here, the authors focus on the role of the gut microbiome in blood pressure regulation and discuss its clinical implications, as well as the challenges and potential of microbiome research.
Hypertension and ageing have deleterious effects on the cerebral microcirculation that can lead to cognitive dysfunction. This Review discusses cerebrovascular maladaptation to hypertension and microvascular contributions to hypertension-induced cognitive impairment in ageing, as well as the role of hypertension in the pathogenesis of Alzheimer’s disease.
The renin–angiotensin system is essential for the regulation of blood pressure and extracellular fluid volume and composition. This Review describes mechanisms that regulate the production of renin in the collecting duct and the local interactions that underlie the contributions of the distal nephron renin–angiotensin system to the pathogenesis of hypertension and kidney injury.
In this Review, the authors discuss the renal mechanism of salt-sensitive hypertension induced by malnutrition during pregnancy, obesity in adult life and ageing. They also describe the epigenetic mechanisms that potentially contribute to the development of salt-sensitive hypertension in these settings.
Hypertension is the leading global cause of cardiovascular disease and premature mortality. In this Review, the authors describe the prevalence, awareness, treatment and control of hypertension worldwide, as well as risk factors for hypertension and the financial burden of this disease.
Hypertension is one of the most common comorbid conditions that is associated with obesity. Here, the authors discuss the complex interactions between renal, hormonal and nervous system factors that link excess adiposity with elevated blood pressure.
Immune mechanisms have important roles in the development of hypertension and end-organ damage. In this Review, David Mattson discusses these mechanisms with a focus on salt-sensitive hypertension and adaptive immunity.
Pre-eclampsia is associated with substantial maternal and fetal morbidity and mortality worldwide. Here, the authors discuss the epidemiology, pathogenesis and current and future treatment of pre-eclampsia with a focus on the role of angiogenic imbalance.
Here, Johnson and Xue describe various physiological and psychosocial challenges that lead to the sensitization of hypertension. These challenges drive neuroplasticity in the brain network controlling sympathetic tone and blood pressure, and provide a new paradigm for understanding essential hypertension.
Increasing evidence suggests an important role of the gut microbiota in the development of hypertension and chronic kidney disease. In this Review, the authors explain their brain–gut–kidney axis hypothesis for the pathogenesis of these diseases.
In this Review, the authors discuss the epidemiology, diagnosis and optimal management of resistant hypertension. They highlight the limitations of clinical trials of device-based therapies conducted to date and propose directions for future research.
The authors present sexual dimorphism at the molecular, cellular and tissue level and suggest that it contributes to differences in disease onset, susceptibility, prevalence and treatment responses in hypertension and cardiovascular disease. Several factors that confer relative cardioprotection in women are discussed, including biological age, sex hormones, sex chromosome complement and lifestyle.
An estimated 10–15% of individuals with hypertension are resistant to available antihypertensive therapies. Findings from two new clinical trials — BrigHTN and PRECISION — that assessed the blood pressure-lowering effects of the aldosterone synthase inhibitor baxdrostat and the dual endothelin receptor antagonist aprocitentan, respectively, suggest these approaches hold promise for patients with treatment-resistant hypertension.
A genetic study using a Mendelian randomization approach provides evidence that albuminuria — as well as being the result of hypertension — might also cause hypertension and cardiometabolic disease. We suggest that a mechanism behind these findings could involve sodium retention by urinary protein-induced activation of the epithelial sodium channel in the distal tubule.
Many considered the failure of the SYMPLICITY HTN-3 trial to represent the end of therapeutic renal denervation. However, promising preliminary data from the SPYRAL HTN-OFF MED study and more recently the SPYRAL HTN-ON MED and RADIANCE-HTN SOLO studies support the efficacy of this intervention for blood pressure lowering in patients with hypertension.
Intensive lowering of blood pressure can decrease the risk of death and cardiovascular events in individuals with hypertension. However, a reanalysis of data from the SPRINT and ACCORD trials suggests that intensive blood pressure lowering increases the risk of chronic kidney disease.
New findings in 2017 enhanced our understanding of the mechanisms that regulate blood pressure. Key studies provided insights into immune mechanisms, the role of the gut microbiota, the adverse effects of perivascular fat and inflammation on the vasculature, and the contribution of rare variants in renin–angiotensin–aldosterone system genes to salt sensitivity.
Uncontrolled hypertension is an important clinical problem and is associated with considerable morbidity and mortality. A new report from the SPYRAL HTN-OFF MED researchers, which describes the use of renal denervation in patients with uncontrolled hypertension, might reignite enthusiasm for this technique, while a first-in-human description of endovascular baroreflex amplification from the CALM-FIM_EUR investigators highlights the potential of this new approach to inhibit sympathetic activity.
Hypertension is a risk factor for chronic kidney disease (CKD), but the optimal blood pressure (BP) target in patients with stage 3–5 CKD is unclear. Now, a meta-analysis reports that more-intensive BP control is associated with a reduced risk of all-cause mortality compared with less-intensive BP goals in this high-risk population.
Pre-eclampsia is a common disorder of pregnancy for which the underlying mechanism is poorly understood. A genome-wide association study has now identified a pre-eclampsia susceptibility locus located near the FLT1 gene. This study brings us a step closer to dissecting the underlying causes of pre-eclampsia.
Renal pericytes have important roles in kidney development, blood pressure regulation and the pathogenesis of kidney disease. Here, the authors review the embryonic development, adult tissue distribution and physiological and pathological roles of the various pericyte subsets in the kidney.
Angiotensin-converting enzyme (ACE) not only plays a major part in the regulation of blood pressure but also participates in several other physiological functions, including renal development and male reproduction. Here, Bernstein et al. discuss how ACE enhances both innate and adaptive responses by modulating macrophage and neutrophil function.
Increasing evidence suggests that renin-expressing cells are involved in a range of physiological processes beyond their traditional role in blood pressure regulation. Here, the authors describe the role of these cells in nephrovascular development, regeneration, oxygen sensing, haematopoiesis and immune responses.