Hypertensive Target Organ Research Articles

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

Role of aldosterone in various target organ damage in patients with hypertensive emergency: a cross-sectional study

BackgroundHypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies.MethodsWe enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed.ResultsAmong 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]).ConclusionIn patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

Racial and Ethnic Disparities in Hypertension Severity and Target Organ Injury at Baseline in Youth Referred for Hypertension Disorders

Racial and Ethnic Disparities in Hypertension Severity and Target Organ Injury at Baseline in Youth Referred for Hypertension Disorders

Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.

Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats. Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II-dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry. Metformin treatment increased the production of short-chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end-diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. Invitro, acetate and propionate altered M1-like gene expression in macrophages, reinforcing anti-inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure. Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.

Abstract P347: Association between Blood Pressure, Left Ventricular Structure and Cognitive Function: Evidence from a Cohort Study in Preschool-aged Children

Objective: Serving as a common hypertensive target organ damage, left ventricular (LV) structure alteration has been found to be associated with cognition decline in the elderly. However, its mediating role in the association between decreased cognitive function and elevated blood pressure (BP) remains controversial, owing to several inherent confounder in adults that could distort observed associations. The study was first known conducted to examine the association between LV structure, BP and cognitive function in preschool-aged children, a population without disturbance of various cardiovascular risk factors. Methods: This study included 1279 children from Shanghai Birth Cohort (SBC) during 2018 to 2021. Using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV), children’s intelligence quotient (IQ) was evaluated at 4-year-old. Detailed anthropometrics and BP measurements and echocardiography were conducted during follow-up. Multivariable linear regression models and restricted cubic spline were applied to estimate the association between individual BP, LV structure parameters and IQ scores. Results: There was no significant association found between cognitive function and LV structure in preschool-aged children, while higher BP levels was found to be correlated with lower scores in cognitive function. Children in the elevated BP and non-LVH group tended to have lower full-scale IQ (FSIQ). In detail, children with elevated BP tended to have lower scores in FSIQ (β: -2.95, 95%CI: -4.65, -1.25), processing speed index (β: -1.77, 95%CI: -3.41, -0.14), working memory index (β: -2.79, 95%CI: -4.70, -0.88) and visual spatial index (β: -2.64, 95%CI: -4.74, -0.55), and these associations were independent of LV structure. Conclusion: Higher BP levels was related to poor cognitive development during childhood as early as four, while LV structure alteration was not. The associations between BP and children’s decreased cognitive function was independent of LV structure.

Renal denervation alleviates vascular remodeling in spontaneously hypertensive rats by regulating perivascular adipose tissue.

Vascular remodeling is the main pathological process that causes the damage of the target organ of hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and plays a key role in the pathogenesis of various cardiovascular diseases. This study aimed to investigate the effects of renal denervation (RDN) on hypertensive vascular remodeling and to elucidate the role of PVAT in this process. Male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were selected. Aortic vascular remodeling was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Morphological changes in the PVAT were observed through H&E and Oil Red O staining. Dihydroethidium was used to measure oxidative stress levels in PVAT, while western blot analysis was used to determine the expression levels of proteins associated with vascular remodeling. The results showed that the aortic medial thickness, media thickness/lumen diameter, collagen volume fraction, and reactive oxygen species (ROS) level in PVAT were significantly higher in the SHR group than in the WKY group. The indexes mentioned above were lower in the SHR-RDN group than in the SHR group. H&E staining revealed that fat droplets in PVAT in the SHR-RDN group became smaller and browning occurred. Moreover, the protein expression of uncoupling protein-1 (UCP-1) and neuregulin 4 (Nrg4) was significantly increased in the SHR-RDN group. In addition, the expression of adiponectin increased and the expression of leptin decreased in the SHR-RDN group compared to the SHR group. In conclusion, RDN can relieve hypertensive vascular remodeling, which may be associated with PVAT.

Risk prediction of pulse wave for hypertensive target organ damage based on frequency-domain feature map

The application of deep learning to the classification of pulse waves in Traditional Chinese Medicine (TCM) related to hypertensive target organ damage (TOD) is hindered by challenges such as low classification accuracy and inadequate generalization performance. To address these challenges, we introduce a lightweight transfer learning model named MobileNetV2SCP. This model transforms time-domain pulse waves into 36-dimensional frequency-domain waveform feature maps and establishes a dedicated pre-training network based on these maps to enhance the learning capability for small samples. To improve global feature correlation, we incorporate a novel fusion attention mechanism (SAS) into the inverted residual structure, along with the utilization of 3 × 3 convolutional layers and BatchNorm layers to mitigate model overfitting. The proposed model is evaluated using cross-validation results from 805 cases of pulse waves associated with hypertensive TOD. The assessment metrics, including Accuracy (92.74 %), F1-score (91.47 %), and Area Under Curve (AUC) (97.12 %), demonstrate superior classification accuracy and generalization performance compared to various state-of-the-art models. Furthermore, this study investigates the correlations between time-domain and frequency-domain features in pulse waves and their classification in hypertensive TOD. It analyzes key factors influencing pulse wave classification, providing valuable insights for the clinical diagnosis of TOD.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

The Pathogenesis and Impact of Arterial Stiffening in Hypertension: The 2023 John H. Laragh Research Award.

Fifty years ago, Dr. John Laragh brought forward the "vasoconstriction-volume hypothesis" of hypertension. This is Ohm's Law in blood pressure regulation, explicating hypertension as a consequence of increased peripheral vascular resistance, cardiac output, or both. Resistance vessels, those of a diameter less than 200 μm, determines mean arterial pressure by controlling peripheral vascular resistance. In comparison, large capacitance arteries, particularly the aorta, confines the systolic and diastolic blood pressure in physiological range through the "windkessel effect." Loss of this cushioning function results in aortic stiffening and isolated systolic hypertension, both of which are independently associated with increased risk for coronary, cerebral, and renal diseases. Aortic stiffening is both a cause and a consequence of hypertension. On one hand, aortic stiffness precedes the onset of hypertension in populations and experimental models, and hemodynamic derangements related to aortic stiffening contributes to the development of hypertension by promoting renal dysfunction. On the other hand, the vasculature itself is a hypertensive target organ and hypertensive mechanical stretch directly induces the pathogenesis of aortic adventitial remodeling. Various cell types, including bone marrow-derived circulating fibrocytes, vascular stem cell antigen-1 positive progenitors, and endothelial to mesenchymal transition, and to a lesser extent resident fibroblasts, contribute to adventitial matrix deposition and aortic stiffening in hypertension. Vascular smooth muscle stiffness is another important contributor of aortic stiffening. Understanding the roles of immune components and specific signal pathways in the pathogenesis aortic stiffening paves the path to novel antihypertensive and anti-fibrosis therapies.

Cognitive impairment in patients with arterial hypertension

Arterial hypertension (AH) is a leading risk factor for cardiovascular diseases including cerebrovascular complications. Strokes and/or vascular cognitive impairment (VCI) are considered as a clinical sign of brain damage as a target organ in hypertension. To identify and assess the severity of VCI, patients with hypertension should undergo a neuropsychological assessment. Neuroimaging confirm the vascular origin of cognitive impairment. Patient management should include antihypertensive therapy along with neuroprotection. Among different neuroprotective therapy, ethylmethylhydroxypyridine succinate (mexidol) is one of medication with serious evidence of clinical efficacy.

Alpha-adducin 1 (rs4961) gene and its expression associated with sodium sensitivity in hypertensive patients: a cohort study in the western Ukrainian population.

Objective. The aim of this study was to evaluate the association of the α-adducin-1 gene (ADD1) (Gly460Trp [rs4961]) polymorphism and its expression in association with renal dysfunction and sodium sensitivity in hypertensive patients in western Ukrainian population. Methods. One-hundred patients with essential arterial hypertension (EAH) and hypertensive-mediated target organ damage (stage 2), moderate, high, and very high cardiovascular risk were enrolled in case-control study. Sixty healthy individuals were assigned as controls. Sodium sensitivity and sodium resistance were determined by salt load reaction. The ADD1 (rs4961) genotyping was performed in RT-PCR. Results. The expression of the quantitative trait loci (eQTL) of ADD1 gene (rs4961) (chr4:2906707 [hg19]) was confirmed in 37 tissues and organs with 23 phenotypic traits. Two hundred eQTL associations revealed - all cis-variants (cis-QTL); 73 methylation QTL (mQTL), 34 splicing QTL (sQTL), 14 histone modification QTL (hQTL), 2 protein QTL (pQTL), 23 transcript utilization QTL (tuQTL), and 4 loci of incorporated long noncoding areas of RNA (lncRNA). GG-genotype unreliably enhances EAH risk (OR=1.92; 95%CI: 0.90-4.10; p=0.066). Sodium sensitivity was observed in 54.0% of patients and in 20.0% of controls (c2=17.89; p<0.001). Sodium sensitivity in T-allele carriers of the ADD1 gene (1378G>T; rs4961) dominated 12-fold in general (OR 95%CI: 2.24-64.29; p=0.001), in women - 4.71 times (OR 95%CI: 1.92-11.56; p<0.001), and in men - 4.09 times (OR 95%CI: 1.03-16.28; p=0.041). Sodium sensitivity elevated the likelihood of severe EAH twice (OR=2.19; OR 95%CI: 1.00-5.05; p=0.049). Conclusion. T-allele associates with sodium sensitivity in essential arterial hypertension patients and increases the risk of hypertension regardless the gender. Sodium sensitivity enhances the probability of severe essential arterial hypertension in observed population.

An Overview on the Mechanisms of Myocardial Damage in Hypertension and the Diagnostic Contribution of Cardiospecific Troponins T and I

Hypertension (HT) is one of the most common cardiovascular (CV) pathologies and a key risk factor for the development of CV disease and its complications. There are two main etiopathogenetic types of HT: primary and secondary. As a result of HT, damage to many organs (heart, blood vessels, retina, etc.) can occur. These organs are considered the main target organs in HT and assessment of their condition plays an important role for optimal management of patients with HT. Increased levels of cardiospecific troponins T and I, localized in the main type of myocardial cells (cardiomyocytes), may indicate myocardial damage. At the same time, the degree of myocardial damage may correlate with the degree of increase in cardiospecific troponins T and I. In recent studies, cardiospecific troponins T and I have established themselves as early and highly specific criteria for myocardial damage not only in myocardial infarction, but also in many other cardiac ( e.g., arrhythmias, endocarditis, myocarditis, takotsubo syndrome, or cardiomyopathy) and extra-cardiac ( e.g., renal failure, sepsis, or diabetes mellitus) conditions. Many authors suggest using cardiospecific troponins T and I as prognostic markers for the above pathologies. Thus, the determination of cardiospecific troponins T and I can provide additional diagnostic advantages in the management of patients with pathological conditions that damage the myocardium. The purpose of this article is to systematize information about the pathogenetic mechanisms of myocardial damage in HT and to consider the diagnostic contribution of cardiospecific troponins T and I for the management of patients with HT.

Association of cognitive impairment and arterial hypertension

Impaired cognitive function (CF) is a common manifestation of brain damage as a target organ of arterial hypertension (AH). The presence of hypertension in middle age increases the risk of developing cognitive impairment (CI) and dementia in old age. At the same time, changes in certain indicators characteristic of AH may serve as predictors of CI and dementia in the future. The review presents data on the effects of endothelial dysfunction and increased arterial stiffness on CF. The small number of papers on the effects of hypertension in middle-aged people on the development of CI emphasizes the importance of investigating this topic, as the incidence of CI in young and middle-aged people has increased in recent years.

The Depiction of Hypertension in Heart Imaging Examinations: An Up-to-Date Review of the Evidence.

Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common hypertensive target organ damages is hypertensive heart disease (HHD), including left ventricular hypertrophy, which progresses gradually and leads to systolic or diastolic dysfunction of the left ventricular, and finally to end-stage heart failure. Regarding its prevalence and the need for early diagnosis, assessment of heart imaging examination is of major importance. Echocardiography has been used as the standard imaging technique to evaluate HHD for years, providing an accurate evaluation of the left ventricular geometry, along with the systolic and diastolic function. However, nowadays there is a growing interest in cardiovascular magnetic resonance (CMR). Despite the importance of the use of echocardiography in everyday clinical practice, numerous studies have shown the superiority of CMR as an imaging technique for clinical and research purposes, mainly due to its strength to provide an unlimited area of view, as well as the identification and quantification of the type and extent of myocardial fibrosis. Hence, this review aims to analyze the importance of heart imaging in the hypertensive population, with a special interest in CMR imaging.

Cognitive impairment in cerebral small vessel disease induced by hypertension.

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease, the most common cerebrovascular disease. However, the causal relationship between hypertension and cerebral small vessel disease remains unclear. Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease. Chronic hypertension and lifestyle factors are associated with risks for stroke and dementia, and cerebral small vessel disease can cause dementia and stroke. Hypertension is the main driver of cerebral small vessel disease, which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction, leukoaraiosis, white matter lesions, and intracerebral hemorrhage, ultimately resulting in cognitive decline and demonstrating that the brain is the target organ of hypertension. This review updates our understanding of the pathogenesis of hypertension-induced cerebral small vessel disease and the resulting changes in brain structure and function and declines in cognitive ability. We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Targeting the NLRP3 inflammasome for the treatment of hypertensive target organ damage: Role of natural products and formulations.

Hypertension is a major global health problem that causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. The mechanisms of hypertensive TOD are not fully understood, and its treatment is challenging. This review provides an overview of the current knowledge on the role of Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in hypertensive TOD and the natural products and formulations that inhibit it. We searched PubMed, Web of Science, Google Scholar, and CNKI for relevant articles using the keywords "hypertension," "target organ damage," "NLRP3 inflammasome," "natural products," and "formulations." We reviewed the effects of the NLRP3 inflammasome on hypertensive TOD in different organs and discussed the natural products and formulations that modulate it. In hypertensive TOD, the NLRP3 inflammasome is activated by various stimuli such as oxidative stress and inflammation. Activation of NLRP3 inflammasome leads to the production of pro-inflammatory cytokines that exacerbate tissue damage and dysfunction. Natural products and formulations, including curcumin, resveratrol, triptolide, and allicin, have shown protective effects against hypertensive TOD by inhibiting the NLRP3 inflammasome. The NLRP3 inflammasome is a promising therapeutic target in hypertensive TOD. Natural products and formulations that inhibit the NLRP3 inflammasome may provide novel drug candidates or therapies for hypertensive TOD. Further studies are needed to elucidate the molecular mechanisms and optimize the dosages of these natural products and formulations and evaluate their clinical efficacy and safety.

Abstract P189.2: Aberrant Trafficking Of Intestinal Immune Cells In Salt-sensitive Hypertension

Hypertension is characterized by an inflammatory response, which precedes the clinical detection of organ damage. Yet, the activation and origin of target organ infiltrating immune cells are not fully understood. This study takes a systems view on inflammation in experimental hypertension and aims to investigate the extent to which the gut-associated immune cells contribute to the immune response in salt-sensitive hypertension. Immune cell trafficking from the intestine to hypertensive target organs was analyzed using in vivo labelling of intestinal immune cells via targeted UV-photoconversion in Kaede -transgenic mice. Salt-sensitive hypertension was induced in 8-10 week old male mice by oral N-nitro-L-arginine methylester (L-NAME) pretreatment (0.5 mg/ml) and two 3-week high-salt feedings (HSD, 4% NaCl-diet, 1% drinking water), separated by a 2-week normal-salt (NSD, 0.5% NaCl-diet) interval. Hypertensive organ damage and photolabelled immune cells (5d post photoconversion) were analyzed. HSD-fed mice displayed target organ damage as indicated by upregulation of mRNA-expression of markers of kidney damage ( Ngal ), inflammation ( Ccl2 ) and fibrosis ( Col3a1 ) (2^-ddCT Sham vs HTN: 1.5±1.3 vs 5.5±3.1, 1.2±0.8 vs 2.7±1.4, 1.0±0.3 vs 2.2±0.7, respectively). Intestinal immune cell trafficking was observed both in homeostasis (NSD) and disease (HSD). Infiltration of photolabelled Kaede red ( Kred+ ) intestinal immune cells was detected in various organs, namely the mesenteric lymph nodes, spleen, blood and bone marrow, as well as target organs of hypertension, namely the kidney, heart and eye. In the kidney, B-cells (39.9 ± 24.2% (NSD), 66.8 ± 5.8% (HSD) of CD45+ Kred+ cells) and T-cells (32.5 ± 18.3% (NSD), 10.1 ± 4.4% (HSD) of CD45+ Kred+ cells) were among the major migrating populations. Salt-sensitive hypertension was characterized by a dysregulation of the intestinal-renal immune cell axis. Immune cells originating from the intestine migrate and populate various organs, both in physiological homeostasis and in an aberrant manner in salt-sensitive hypertension. Our findings provide insight into mechanisms underlying hypertension-induced organ damage and could argue for interventions targeting intestinal immune cells.

Antihypertensive activity of different components of Veratrum alkaloids through metabonomic data analysis

BackgroundHypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 – 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions. PurposeThis study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action. ResultsTotal Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension. ConclusionThis work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO–ET homeostasis.

Mouse models of cerebral injury and cognitive impairment in hypertension.

Hypertension is a major risk factor for dementia, including both vascular and neurodegenerative etiologies. With the original aim of studying the effect of blood pressure elevation on canonical target organs of hypertension as the heart, the vasculature or the kidneys, several experimental models of hypertension have sprouted during the years. With the more recent interest of understanding the cerebral injury burden caused by hypertension, it is worth understanding how the main models of hypertension or localized cerebral hypertension stand in the field of hypertension-induced cerebral injury and cognitive impairment. With this review we will report main genetic, pharmacological and surgical models of cognitive impairment induced by hypertension, summarizing how each specific category and model can improve our understanding of the complex phenomenon of cognitive loss of vascular etiology.

Antihypertensive, antioxidant, and renal protective impact of integrated GJD with captopril in spontaneously hypertensive rats

Hypertension is the most prevalent chronic disease World-wide, and the leading preventable risk factor for cardiovascular disease (CVD). Few patients accomplish the objective of decreasing blood pressure and avoiding hypertensive target organ damage after treatments with antihypertensive agents which opens the door for other treatments, such as herbal-and antihypertensive combination therapy. Captopril (CAP), as a-pril which inhibits angiotensin converting enzyme has long been used in the management of hypertension and CVD. Gedan Jiangya Decoction (GJD) is known for antihypertensive effects in prior studies. The research is aimed to determine whether GJD in combination with captopril has antihypertensive, kidney protective, antioxidant, and vasoactive effects in spontaneously hypertensive rats (SHR). Regular measurements of systolic and diastolic blood pressure (SBP and DBP), and body weight were monitored weekly. H&E staining was utilized to examine histopathology. The combined effects were studied using ELISA, immunohistochemistry, and qRT-PCR. Significant reductions in SBP, DBP, aortic wall thickness, and improvement in renal tissue were observed following GJD + CAP treatment, with increased serum levels of NO, SOD, GSH-Px, and CAT and decreases in Ang II, ET-1, and MDA. Similarly, GJD + CAP treatment of SHR's significantly decreased ET-1 and AGTR1 mRNA and protein expression while increasing eNOS mRNA and protein expression in thoracic aorta and kidney tissue. In conclusion, the present investigation found that GJD + CAP treatment decreases SHR blood pressure, improves aorta remodeling and renal protection, and that this effect could be attributable, in part, due to antioxidant and vascular tone improvement.