Hypertension-induced Target Organ Damage Research Articles

Abstract P305: MACHINE LEARNING DETECTS ASSOCIATIONS BETWEEN RETINA FEATURES AND BLOOD PRESSURE STATUS IN RICE DIET PROGRAM PATIENTS

The retina provides direct evidence of target-organ damage, and in hypertension, it may reflect vascular disease status in conjunction with clinical measurement of blood pressure (BP). However, outcomes of the examination of the retina varies from one clinician to another due to various reasons. Machine learning methods have been used as a supportive tool in identifying deep retina features objectively and consistently. The Kempner Rice Diet Program, developed in the early 1940s, used a low-salt and low-protein diet intervention (Rice Diet) to treat patients with severe hypertension before effective drug treatment was available. The meticulously documented medical records of the Rice Diet Program patients and their retina photographs provide a rare opportunity to examine the association of BP trajectories and target-organ damage as reflected in the retina. We trained a deep neural network on systolic BP and funduscopic changes from the UK Biobank Project. We achieved an R 2 value of 0.36 on 16,357 validation retina images from the UK Biobank. Our model predicts BP values for specific retinal areas by producing heatmaps of higher or lower hypertensive findings. We then applied the model on 975 retina photographs of 165 patients of the Rice Diet Program. We observed a significant correlation between retina features and systolic BP (Correlation= 0.35, p = 2*10 -29 ), showing that the model generalizes to patients with hypertension and images taken under a variety of conditions between 1944-1971. We suggest that deep-learning-based predictions for retinal analysis could be useful in monitoring treatment progress and recovery from hypertension-induced target-organ damage. This assessment serves as an adjunct to point-of-care BP measurements in the subset of 165 patients. Our findings underscore the potential utility of machine learning in hypertension evaluation and treatment. Further, it may allow us to elucidate individual responses to hypertension treatment beyond BP measurement alone. Findings from this first-step analysis may promote development of more effective BP control strategies.

Abstract 124: Angiotensin-(1-12) Immunoneutralization: A New Approach To Hypertension Treatment

There is a critical need to identify new therapeutic targets and treatments, given emerging data documenting the limited effectiveness of current antihypertensive drugs to have a marked impact in preventing target organ damage and cardiovascular death. While monoclonal antibodies (mAb) are revolutionizing the treatment of human diseases, including severe hypercholesterolemia, their applicability to long-term hypertension control remains unexplored. Identification of angiotensin-(1-12) [Ang-(1–12)] as a non-renin-dependent substrate for Ang II generation in rodents and humans led us to engineer a mAb directed against the C-terminus of human Ang-(1–12) [h-Ang-(1-12)] sequence. We utilized a model of hypertension expressing the human angiotensinogen (AGT) gene in the rat genome [TGR(hAGT)L1623 rats] to address the effectiveness of endogenous h-Ang-(1–12) immunoneutralization in controlling the elevated blood pressure and reversing hypertension-induced target organ damage. Acute delivery of the h-Ang-(1–12) mAb (30 mg/Kg, i.v.) in anesthetized hypertensive transgenic rats induced a prompt arterial pressure fall (M ± SE: -18 ± 6/-16 ± 3 mm Hg, n=7; p< 0.001) in the absence of corresponding heart rate changes. The antihypertensive effect of the h-Ang-(1-12) mAb triggered a rise in plasma renin concentrations (from 107 ± 24 to 381 ± 260 ng/mL/h) that was inversely correlated with the fall in mean arterial pressure (r= -0.92, p< 0.001). Prior intravenous delivery of aliskiren fumarate (3-5 mg/Kg, i.v.) while inducing a fall in arterial pressure did not mask the antihypertensive action of the h-Ang-(1-12) mAb. Extension of these acute effects of the h-Ang-(1-12) mAb to awake instrumented transgenic hypertensive rats given consecutive daily doses of the mAb (30 mg/Kg, i.m. x 4 -5 days, n=7) documented a trend for significant statistical drops in daytime blood pressure and no changes in heart rate. We conclude that Ang-(1–12) is an endogenous Ang II forming substrate participating in the control of arterial pressure in a humanized model of high blood pressure and that selective immunoneutralization of this alternate substrate is a promising and novel therapeutic approach to treat hypertension and prevent its adverse cardiovascular sequelae.

Inadequate hypertension control rates: A global concern for countries of all income levels.

Inadequate hypertension control rates: A global concern for countries of all income levels.

LOWER CIRCULATING MIR-191-5P AND LET-7G-5P ARE INDEPENDENT BIOMARKERS OF RENAL INJURY

Objective: Hypertension is associated with subclinical target organ damage including cardiac, vascular and kidney injury. Circulating microRNAs have been investigated as biomarkers of cardiovascular disease, but few studies have examined them as target organ damage biomarkers in hypertension. We aimed to identify circulating microRNAs that could serve as biomarkers of hypertension-induced target organ damage using an unbiased approach. Design and method: Normotensive subject, hypertensive patients (HTN) and patients with HTN associated with at least 2 other features of the metabolic syndrome (MetS) or with chronic kidney disease (CKD) grades 3–4 were studied (n = 15–16). Blood pressure was determined by automated office measurement (AOBP). Blood and urine were collected for determination of blood cell count, blood biochemistry and urinalysis. Platelet-free plasma (6 mL) was isolated from blood collected on EDTA, and RNA extracted for small RNA deep sequencing using Illumina HiSeq-2500. Differentially expressed (DE) genes were identified with a threshold of false discovery rate < 0.1. The most abundant DE miRNAs were confirmed by reverse transcription-quantitative PCR (RT-qPCR). Right common carotid artery remodeling and stiffness were assessed by ultrasound and aorta stiffness by carotid to femoral pulse wave velocity. Results: We found 4 up-regulated and 4 down-regulated miRNAs uniquely associated with the HTN group, 1 up-regulated uniquely associated with the MetS group, 1 up-regulated and 12 down-regulated miRNAs uniquely associated with the CKD group and 8 were found similarly DE in different groups (P < 0.01 and q < 0.1). Two down-regulated miRNAs, let-7g-5p and miR-191–5p of 11, the most abundant DE miRNAs, were validated by RT-qPCR. Correlation analysis revealed that let-7g-5p was associated with large vessel stiffening, miR-191–5p with diabetes, and both microRNAs with estimated glomerular filtration rate (eGFR) and inflammatory markers. Using let-7g-5p and miR-191–5p and parameters that correlated with eGFR as candidate variables, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191–5p and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.40 (P = 1.1e-5). Conclusions: Circulating let-7g-5p and miR-191–5p were identified as independent biomarkers of chronic kidney disease among patients with hypertension, which could have pathophysiological and therapeutic implications.

Effects of inhibition of the renin-angiotensin system on hypertension-induced target organ damage: clinical and experimental evidence.

The dysregulation of renin-angiotensin-system (RAS) plays a pivotal role in hypertension and in the development of the related target organ damage (TOD). The main goal of treating hypertension is represented by the long-term reduction of cardiovascular (CV) risk. RAS inhibition either by angiotensin converting enzyme (ACE)-inhibitors or by type 1 Angiotensin II receptors blockers (ARBs), reduce the incidence of CV events in hypertensive patients. Actually, ACE-inhibitors and ARBs have been demonstrated to be effective to prevent, or delay TOD like left ventricular hypertrophy, chronic kidney disease, and atherosclerosis. The beneficial effects of RAS blockers on clinical outcome of hypertensive patients are due to the key role of angiotensin II in the pathogenesis of TOD. In particular, Angiotensin II through an inflammatory-mediated mechanism plays a role in the initiation, progression and vulnerability of atherosclerotic plaque. In addition, Angiotensin II can be considered the hormonal transductor of the pressure overload in cardiac myocytes, and through an autocrine-paracrine mechanism plays a role in the development of left ventricular hypertrophy. Angiotensin II by modulating the redox status and the immune system participates to the development of chronic kidney disease. The RAS blocker should be considered the first therapeutic option in patients with hypertension, even if ACE-inhibitors and ARBs have different impact on CV prevention. ARBs seem to have greater neuro-protective effects, while ACE-inhibitors have greater cardio-protective action.

Evaluation of microalbuminuria in patients with hypertension from North Indian population: A case-control study

Introduction: Microalbuminuria has recently emerged as an early marker of hypertension induced target organ damage. Microalbuminuria in hypertensive patients may act as a potential risk factor for cardiovascular and kidney diseases. Objective:The aim of the study is to evaluate the levels of microalbuminuria in hypertensive (HT) patients and normotensive (NT) control subjects. Materials and Methods:In this case-control study, 42 HT patients and 42 age and gender matched NT controls were enrolled. Body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP) was measured by standard protocol. Urinary microalbumin and creatinine were estimated in spot urine sample of all subjects using commercially available kit. Chi-square test, unpaired t test and Pearson correlation coefficient were used for Statistical analysis. The p-value Results:In this study, results showed that more than half of the HT patients have smoking habits (59.3%), alcoholic habits (71.4%) and family history of HT (73.8%), which is significantly higher as compared to NT controls (p=0.02, p=0.004, p=0.02, respectively). Anthropometric parameters height, weight and BMI were found significantly higher in HT patients as compared to NT controls (p=0.01, p=0.007, p=0.001, respectively). Mean of SBP and DBP were also found significantly higher in HT patients than NT controls (p=0.001, p=0.001, respectively). Urinary microalbumin, urinary creatinine and albumin creatinine ratio (ACR) were found significantly higher in HT patients as compared to NT controls (p=0.02, p=0.01, p=0.02, respectively). Correlation of various anthropometric and clinical parameters showed that ACR have significantly positive correlation with age in HT patients (r=0.364, pnegative correlation with age in HT patients, but not significant (r= -0.027). Similarly, ACR also have negative correlation with BMI, SBP and DBP in HT patients (r= -0.068, r= -0.145, r= -0.219, respectively), but these are not significant. Conc

AdipoRon Attenuates Hypertension-Induced Epithelial-Mesenchymal Transition and Renal Fibrosis via Promoting Epithelial Autophagy.

Hypertension-induced epithelial-mesenchymal transition (EMT) is a major mechanism of renal fibrosis. Adiponectin protects against hypertension-induced target organ damage. AdipoRon is an orally active synthetic adiponectin receptor agonist. However, it is unclear whether AdipoRon could attenuate EMT and renal fibrosis in hypertensive mice. C57BJ/6J mice were utilized to induce DOCA-salt-sensitive hypertensive model. Hypertension results in an altered adiponectin expression and promotes EMT in the kidney. In vitro, AdipoRon inhibits aldosterone (Aldo)-induced EMT and promotes autophagic flux in HK-2 epithelial cells. Mechanically, AdipoRon activates AMPK/ULK1 pathway in epithelial cells. Blockade of AMPK activation, as well as inhibition of autophagy, blocks the effects of AdipoRon on Aldo-induced EMT. Moreover, AdipoRon treatment promotes autophagy and improves renal fibrosis in DOCA-salt-hypertensive mice. Our data suggest that AdipoRon could be a potential therapeutic option to prevent renal fibrosis in hypertensive patients. Graphical abstract.

Insulin Resistance the Hinge Between Hypertension and Type 2 Diabetes.

Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes.

Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK

IntroductionArterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary...

Ambulatory Blood Pressure Phenotypes in Children and Adolescents

Ambulatory Blood Pressure Phenotypes in Children and Adolescents

Treatment of Hypertension Induced Target Organ Damage in Children and Adolescents.

High blood pressure in children and adolescents may have an adverse impact on the heart, the vessels, the kidney, and the central nervous system causing early functional or structural changes. The most prevalent subclinical hypertensive target organ damage in children and adolescents is left ventricular hypertrophy, and echocardiographic assessment of left ventricular mass is suggested in all hypertensive children. There is evolving evidence that antihypertensive treatment in children and adolescents could lead to regression of target organ damage, emphasizing also the importance of adequate blood pressure control. Assessment of subclinical organ damage could guide clinical decisions from diagnosis with regard to intensity non-pharmacological treatment, time to wait for initiation of pharmacological treatment, and choice of drug. Longitudinal studies are needed to relate the effectiveness of antihypertensive treatment and blood pressure targets in childhood with future cardiovascular or renal events. This review summarizes evidence on the associations of hypertension with target organ damage in children and adolescents and the role of antihypertensive therapy on the regression of target organ damage in the pediatric age group.

Chios mastic gum decreases renin levels and ameliorates vascular remodeling in renovascular hypertensive rats.

Chios mastic gum (CMG) exerts robust anti-inflammatory and antioxidant properties and it affects pathways that are implicated in the pathophysiology of endothelial and vascular inflammation. Aim of this study was to test the hypothesis that CMG administration lowers blood pressure (BP) and improves hypertension-induced target organ damage. 2-kidney, 1-clip (2K1C) hypertensive rats were treated with CMG (40 mg/kg body weight/day) for 2-weeks after the establishment of hypertension. Acute CMG administration lowered systolic, diastolic and mean arterial BP, while these hemodynamic effects were sustained throughout the 2-week administration period. CMG group also exhibited alleviated target organ damage as proposed by amelioration of biomechanical properties of the aorta -including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. The anti-hypertensive effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis indicated that the effect of CMG on organ damage was BP-lowering dependent and was not associated with direct effects of renin or with its anti-inflammatory properties. We suggest a BP lowering effect of CMG via down-regulation of renin excretion associated with attenuation of target organ damage and inflammatory status. These observations provide profound evidence for the beneficial role of CMG in hypertension, which could possibly translate to further clinical research.

ACUTE AND CHRONIC EFFECTS OF CHIOS MASTIC GUM ON BLOOD PRESSURE IN A RODENT MODEL OF 2-KIDNEY 1-CLIP HYPERTENSION

Objective: Chios mastic gum (CMG), a Greek plant resin, has been studied for its protective role against endothelial and vascular inflammation by suppressing oxidative stress and downregulating the expression of pro-inflammatory mediators. Objective: We sought to investigate the effect of CMG administration on blood pressure (BP) and hypertension-induced target organ damage. Design and method: 16-week-old male Wistar rats were allocated into 3 groups: Control group; 2-kidney, 1-clip (2K1C) group; CMG group which was treated with CMG (40 mg/kg body weight /day) for 2-weeks after the establishment of hypertension. Results: Acute CMG administration led to a decrease in systolic, diastolic and mean arterial BP (153 vs 188 mmHg, 108 vs 141 mmHg and 122 vs 156 mmHg for CMG and 2K1C groups, respectively), while these hemodynamic effects were sustained throughout the 2-week administration period (136 vs 194 mmHg, 100 vs 141 mmHg and 112 vs 159 mmHg for CMG and 2K1C groups, respectively. CMG also attenuated target organ damage as proposed by amelioration of biomechanical properties of the aorta –including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. Furthermore, CMG administration was associated with decreased interleukin-6 (IL-6) and C-reactive protein (CRP) levels. The BP lowering effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis showed that the amelioration of organ damage was BP-lowering dependent and was not correlated with direct effects of renin or with its anti-inflammatory properties. Conclusions: Our results indicate an anti-hypertensive effect of CMG via down-regulation of renin excretion and suppression of the inflammatory cascade associated with alleviation of target organ damage. These observations provide substantial evidence for the potentially beneficial role of CMG in treating hypertension, yet clinical translation studies are further required.

Multiplicative interaction between mean corpuscular volume and red cell distribution width with target organ damagein hypertensive patients.

Accumulating evidence suggests that increased red cell distribution width (RDW) and mean corpuscular volume (MCV) were both poor prognostic factors for patients with cardiovascular diseases. Recently, the multiplicative interaction between RDW and MCV has been observed for predicting mortality in elderly patients without anemia; however, the relationship between the product of RDW-MCV and hypertension-induced target organ damage (TOD) has not been evaluated. We performed a cross-sectional study in 1115 hypertensive patients. RDW and MCV were determined using automated hematology analyzers. Prevalence of TOD was evaluated by estimated glomerular filtration rate, carotid intima-media thickness, and left ventricular mass index. The prevalence of TOD was observed to be increased with the RDW or product of RDW-MCV quartiles. Moreover, RDW, MCV and product of RDW-MCV were significantly higher in patients with TOD compared to those without TOD. According to two logistic regression models, the associations of RDW and MCV with TOD were lost after adjustment for other factors. However, product of RDW-MCV remains an independent predictor of TOD, with per 0.4fL increase in the product of RDW-MCV associated with a 16% increased risk of TOD (P=.012). The inclusion of MCV by calculating the product of RDW-MCV appears to enhance the association of RDW with TOD.

Cardiac-deleterious role of galectin-3 in chronic angiotensin II-induced hypertension.

Galectin-3 (Gal-3), a member of the β-galactoside lectin family, has an important role in immune regulation. In hypertensive rats and heart failure patients, Gal-3 is considered a marker for an unfavorable prognosis. Nevertheless, the role and mechanism of Gal-3 action in hypertension-induced target organ damage are unknown. We hypothesized that, in angiotensin II (ANG II)-induced hypertension, genetic deletion of Gal-3 prevents left ventricular (LV) adverse remodeling and LV dysfunction by reducing the innate immune responses and myocardial fibrosis. To induce hypertension, male C57BL/6J and Gal-3 knockout (KO) mice were infused with ANG II (3 μg·min-1·kg-1 sc) for 8 wk. We assessed: 1) systolic blood pressure by plethysmography, 2) LV function and remodeling by echocardiography, 3) myocardial fibrosis by histology, 4) cardiac CD68+ macrophage infiltration by histology, 5) ICAM-1 and VCAM-1 expression by Western blotting, 6) plasma cytokines, including interleukin-6 (IL-6), by enzyme-linked immunosorbent assay, and 7) regulatory T (Treg) cells by flow cytometry as detected by their combined expression of CD4, CD25, and FOXP3. Systolic blood pressure and cardiac hypertrophy increased similarly in both mouse strains when infused with ANG II. However, hypertensive C57BL/6J mice suffered impaired ejection and shortening fractions. In these mice, the extent of myocardial fibrosis and macrophage infiltration was greater in histological sections, and cardiac ICAM-1, as well as plasma IL-6, expression was higher as assessed by Western blotting. However, all these parameters were blunted in Gal-3 KO mice. Hypertensive Gal-3 KO mice also had a higher number of splenic Treg lymphocytes. In conclusion, in ANG II-induced hypertension, genetic deletion of Gal-3 prevented LV dysfunction without affecting blood pressure or LV hypertrophy. This study indicates that the ANG II effects are, in part, mediated or triggered by Gal-3 together with the related intercellular signaling (ICAM-1 and IL-6), leading to cardiac inflammation and fibrosis.

Clinical effects of phosphodiesterase 3A mutations in inherited hypertension with brachydactyly.

Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator-stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population.

Hypertension criterion for stroke prevention--to strengthen the principle of individualization in guidelines.

The diagnosis of hypertension, as recommended by most guidelines, is determined by systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. A threshold-based definition of hypertension, however, ignores sex and age, pathophysiology, and disparities in patient-specific conditions. Moreover, the harmful effects of hypertension-induced target organ damage cannot be ignored. Although the principle of individualization for hypertension management is recommended, especially for stroke prevention, how to practice it in a clinical setting has not been clearly elaborated. Therefore, we put forward a proposal for individualized hypertension management incorporating target organ damage, the main harmful effect of hypertension. We propose that hypertension should be diagnosed when an individual's blood pressure exceeds some difference from their own baseline in young adulthood, accompanied by any hypertension-induced target organ damage, confirmed by various detection methods. Application of this proposal to stroke prevention will hopefully strengthen the principle of individualized hypertension management.

Mesenchymal stem cells seem too good to believe!

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into various cell types including osteoblasts, chondroblasts, adipocytes, vascular smooth muscle cells, and other cell types (Fig. 1). MSCs harbor unique immunomodulatory properties and therefore hold great promise in tissue engineering, since they not only directly participate in tissue regeneration and repair but also modulate the host’s foreign body responses [1]. The signaling pathways regulating MSCs include bone morphogenetic proteins (BMPs), epidermal growth factors (EGF), transforming growth factors (TGF), wingless integration site (wnt) proteins, fibroblastic growth factor (FGF), and transcription factors, and have been reviewed earlier [2]. MSCs can maintain antiinflammatory, anti-fibrotic, antimicrobial, and regenerative properties, so that they could conceivably improve outcomes in various conditions featuring damaged tissues and inflammation [3]. The putative beneficial effects of MSCs include increased cell survival and proliferation, decreased inflammation, and suppression of immune function. With such a broad magical repertoire of effects, how could they miss? Failures have hardly been reported. Could MSCs lower blood pressure or ameliorate hypertension-induced target-organ damage? MSCs have been injected into stroke-prone spontaneously hypertensive rats (SHR). The authors of that report claimed that MSCs had antioxidant and anti-apoptotic effects as well as the ability to repair hippocampal damage in SHR [4]. However, a reduction in blood pressure was not reported. Other investigators injected MSCs into tail veins of rats subjected to 2-kidney, 1-clip renovascular hypertension [5]. MSCs prevented the progressive increase in blood pressure, ameliorated targetorgan damage, reduced fibrosis, proteinuria, and inflammatory cytokines, suppressed the intrarenal renin-angiotensin system, decreased sympathetic hyperactivity, and infiltrated not only the kidneys but also the central nervous system in the rats. These are remarkable claims indeed! Investigators have also applied MSCs to models of renal disease [6, 7]. In this issue of J Mol Med, Hu and colleagues treated Dahl salt-sensitive (S) rats with intrarenal MSCs [8]. Immunohistochemistry and flow-cytometry analyses showed a significantly reduced number of stem cell marker CD133+ cells in the renal medulla of Dahl S rats, compared to controls, suggesting a renal stem-cell deficiency. Rat MSCs or control cells were transplanted into the renal medulla in uninephrectomized Dahl S rats. High-salt diet resulted in sodium retention and hypertension in control Dahl S rats. These effects were significantly attenuated in MSC-treated

Hypertension-induced target organ damage and early identification in children

Hypertension is a global problem,affecting both developed and developing nations. The morbidity of hypertension in children and adolescents has increased year by year in recent years. Hypertension in children can cause target organ damages（mainly renal,cardiovascular,central neurological,or optic fundal）. In clinical practice,we need to find simple and easy methods for early recognition of target organ damages,thus serious consequences in adult hypertension may be prevented. Key words: Hypertension; Target organ damage; Early identification; Children

Immune-related effects in hypertension and target-organ damage

Several studies published in the past three decades have suggested that inflammation and activation of immunity are central features in the pathogenesis of atherosclerosis, ischemic myocardial injury, and also in hypertension-induced target organ damage. A better understanding of this field could help us to explain the increased cardiovascular risk in patients with chronic inflammation. Recent studies have demonstrated that macrophages and various T-cell subtypes play a pivotal role in the regulation of blood pressure and target organ damage. Hypertensive stimuli such as the effector molecule of the renin-angiotensin system, angiotensin II, not only regulate vascular tone and sodium balance, but also activate immune cells and promote cell infiltration into target organs. Experimental and clinical evidence show that adaptive transfer of immune cells, rendering mice deficient for a certain subset of immune cells, or immunosuppressive treatment affects blood pressure and ameliorates target organ damage. The aim of this review is to summarize and discuss some of the more recent insights as to how immune cells might affect the regulation of blood pressure and the pathogenesis of hypertension-induced target organ damage.