Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Mechanism and functional substances of Saiga antelope horn in treating hypertension with liver-yang hyperactivity syndrome explored using network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. MATERIALS AND METHODS: The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. RESULTS: SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. CONCLUSIONS: Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.

Enhancing the therapeutic potential of isoliensinine for hypertension through PEG-PLGA nanoparticle delivery: A comprehensive in vivo and in vitro study.

BACKGROUND: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. RESULT: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. CONCLUSION: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. SIGNIFICANCE: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.

Study on material basis and anti-hypertensive metabolomics of Zhengan-Xifeng-Tang(ZXT): A comparison between ZXT decoction and granules.

High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients.

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Lycorine inhibits Ang II-induced heart remodeling and inflammation by suppressing the PI3K-AKT/NF-κB pathway.

BACKGROUND: Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. METHODS: Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. RESULTS: LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. CONCLUSION: Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.

Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS: A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS: Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS: The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.

Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension.

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements included nitrate and nitrite in plasma and saliva; endothelial-dependent and -independent forearm blood flow (FBF) responses to acetylcholine (FBFACh) and glyceryltrinitrate (FBFGTN); and clinic-, home- and 24-hour ambulatory blood pressure. Compared to placebo, plasma and salivary nitrate and nitrite increased at 3H and 4WK POST following nitrate treatment (P < 0.01), suggesting a functioning nitrate-nitrite-NO pathway in the participants of this study. There were no differences between treatments in FBFACh and FBFGTN-area under the curve (AUC) ratios [AUC ratios after (3H POST, 4WK POST) compared with before (PRE) the intervention], or 24-hour ambulatory blood pressure or home blood pressure measures (P > 0.05). These findings do not support the hypothesis that an increased intake of dietary nitrate exerts sustained beneficial effects on FBF or blood pressure in hypertensive older adults, providing important information on the efficacy of nitrate-based interventions for healthy vascular aging. This study was registered under ClinicialTrials.gov (NCT04584372).

Efficacy and safety of chinese herbal foot bath for hypertension: A systematic review and meta-analysis.

BACKGROUND: Hypertension is a prevalent condition with significant impacts on human health. Chinese herbal foot bath, a traditional Chinese medicine treatment, is believed to help manage hypertension. OBJECTIVE: This systematic review aims to assess the efficacy of combining Chinese herbal foot bath with conventional treatment for hypertension. METHODS: A thorough search across eight databases was conducted to identify relevant studies on Chinese herbal foot bath for hypertension. Randomized controlled trials examining the benefits and risks of using Chinese herbal foot bath combined with conventional treatment for hypertension were included. Blood pressure changes before and after the Chinese herbal foot bath were assessed, and outcomes were analyzed using Review Manager 5.3 software. The certainty of evidence was evaluated using the GRADE tool. RESULTS: Compared to conventional treatment, Chinese herbal foot bath combined with conventional treatment demonstrated greater effectiveness in reducing systolic blood pressure (MD 6.69, 95% CI: 5.86 to 7.53, p < 0.00001) and diastolic blood pressure (MD 5.83, 95% CI: 5.23 to 6.43, p < 0.00001), which reported fewer adverse effects.These studies commonly present issues such as inadequate randomization, lack of blinding, and absence of independent testing for the purity or potency of herbs. CONCLUSION: The meta-analysis suggests that Chinese herbal foot bath combined with conventional treatment may effectively manage hypertension, with few adverse effects. However, high-quality clinical trials are still needed to confirm these findings due to methodological weaknesses in randomization, blinding, long-term follow-up, and independent testing for the purity and potency of herbs.

IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia.

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 wk of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the Reduced Uterine Perfusion Pressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized that IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted intraperitoneal mini-osmotic pumps infusing recombinant rat IL-33 (1 µg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14 to 19. We found that IL-33 supplementation in RUPP rats reduces maternal blood pressure and improves the uterine artery resistance index (UARI). In addition to physiological improvements, we found decreased circulating and placental cytolytic Natural Killer cells (cNKs) and decreased circulating, placental, and renal TH17s in IL-33-treated RUPP rats. cNK cell cytotoxic activity also decreased in IL-33-supplemented RUPP rats. Furthermore, renal ROS and placental preproendothelin-1 (PPET-1) decreased in RUPP rats treated with IL-33. These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, renal ROS, and PPET-1 expression. These data suggest that IL-33 may have therapeutic potential in managing PE.NEW & NOTEWORTHY Though decreased IL-33 signaling has been clinically associated with PE, the mechanisms linking this signaling pathway to overall disease pathophysiology are not well understood. This study provides compelling evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction observed in response to placental ischemia, such as in PE. Data presented in this study submit the IL-33 signaling pathway as a possible therapeutic target for the treatment of PE.

Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). AIM OF THE STUDY: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. MATERIALS AND METHODS: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. RESULTS: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. CONCLUSION: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Relationship of Blood Pressure, Health Behaviors, and New Diagnosis and Control of Hypertension in the BP-CHECK Study.

BACKGROUND: Undiagnosed hypertension and uncontrolled blood pressure (BP) are common and contribute to excess cardiovascular morbidity and mortality. We examined whether BP control, changes in BP, and patient behaviors and attitudes were associated with a new hypertension diagnosis. METHODS: We performed a post hoc analysis of 323 participants from BP-CHECK (Blood Pressure Checks for Diagnosing Hypertension), a randomized diagnostic study of BP measuring methods in adults without diagnosed hypertension with elevated BP recruited from 12 primary care clinics of an integrated health care system in Washington State during 2017 to 2019. All 323 participants returned a positive diagnostic test for hypertension based on 24-hour ambulatory BP monitoring and were followed for 6 months. We used linear regression to examine the relationships between a new hypertension diagnosis (primary independent variable) and differences in the change in study outcomes from baseline to 6-month. RESULTS: Mean age of study participants was 58.3 years (SD, 13.1), 147 (45%) were women, and 253 (80%) were of non-Hispanic White race. At 6 months, 154 of 323 (48%) participants had a new hypertension diagnosis of whom 88 achieved target BP control. Participants with a new hypertension diagnosis experienced significantly larger declines from baseline in BP (adjusted mean difference: systolic BP, -7.6 mm Hg [95% CI, -10.3 to -4.8]; diastolic BP, -3.8 mm Hg [95% CI, -5.6 to -2.0]) compared with undiagnosed peers. They were also significantly more likely to achieve BP control by 6 months compared with undiagnosed participants (adjusted relative risk, 1.5 [95% CI, 1.1 to 2.0]). At 6 months, 101 of 323 participants (31%) with a positive ambulatory BP monitoring diagnostic test remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications. CONCLUSIONS: Approximately one-third of participants with high BP on screening and ambulatory BP monitoring diagnostic testing remained with undiagnosed hypertension, uncontrolled BP, and no antihypertensive medications after 6 months. New strategies are needed to enhance integration of BP diagnostic testing into clinical practice. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03130257.

Sinapine targeting PLCß3 EF hands disrupts Gαq-PLCß3 interaction and ameliorates cardiovascular diseases.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.

Acute Effects of Coffee Consumption on Blood Pressure and Endothelial Function in Individuals with Hypertension on Antihypertensive Drug Treatment: A Randomized Crossover Trial.

INTRODUCTION: Coffee is a complex brew that contains several bioactive compounds and some of them can influence blood pressure (BP) and endothelial function (EF), such as caffeine and chlorogenic acids (CGAs). AIM: This study aimed to evaluate the acute effects of coffee on BP and EF in individuals with hypertension on drug treatment who were habitual coffee consumers. METHODS: This randomized crossover trial assigned 16 adults with hypertension to receive three test beverages one week apart: caffeinated coffee (CC; 135 mg caffeine, 61 mg CGAs), decaffeinated coffee (DC; 5 mg caffeine, 68 mg CGAs), and water. BP was continuously evaluated from 15 min before to 90 min after test beverages by digital photoplethysmography. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluated EF before and at 90 min after test beverages. At the same time points, microvascular reactivity was assessed by laser speckle contrast imaging. Repeated-measures-ANOVA evaluated the effect of time, the effect of beverage, and the interaction between time and beverage (treatment effect). RESULTS: Although the intake of CC produced a significant increase in BP and a significant decrease in RHI, these changes were also observed after the intake of DC and were not significantly different from the modifications observed after the consumption of DC and water. Microvascular reactivity did not present significant changes after the 3 beverages. CONCLUSION: CC in comparison with DC and water neither promoted an acute increase in BP nor produced an improvement or deleterious effect on EF in individuals with hypertension on drug treatment who were coffee consumers.

Should echocardiogram be undertaken routinely when a child has severe iron deficiency anaemia?

Iron deficiency anaemia (IDA) is common in children. Treatment usually consists of oral iron therapy and, if severe, inpatient hospitalisation with blood transfusion. Providers may also undertake an echocardiogram, depending on availability and the severity of anaemia. A male toddler with nutritional IDA, haemoglobin of 1.7 g/dL (the lowest level in the literature) and hypertension had left ventricular hypertrophy (LVH) on the initial echocardiogram. He was managed acutely with judicious blood transfusion, followed by oral iron supplementation and anti-hypertensive medication at discharge. Repeat echocardiogram a month later demonstrated slight improvement of the LVH but the hypertension persisted at follow-up 6 months later. There was complete resolution of the findings a year later. In chronic nutritional IDA, there can be structural cardiac changes which can affect the acute management and requires close follow-up. It is important to use echocardiography in such severe cases.Abbreviations: CHF: congestive heart failure; CM: cardiomyopathy; DCM: dilated cardiomyopathy; ICU: intensive care unit; IDA: iron deficiency anaemia; IVSd: interventricular septum in diastole; LA: left atrium; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; LVH: left ventricular hypertrophy; LVM: left ventricular mass; LVPWd: left ventricular posterior wall end-diastole; PRBC: packed red blood cells.

Uncovering the mechanism of Naoxintong capsule against hypertension based on network analysis and in vitro experiments.

Naoxintong capsule (NXT) is a clinical drug for the treatment of cardiovascular diseases, but its pharmacological mechanism against hypertension remains unclear. Data concerning the compounds and targets of NXT were obtained from the TCMSP and DrugBank, whereas data concerning hypertension-related genes were obtained from DisGeNET. The network was analyzed and established by STRING and Cytoscape, and function enrichment was analyzed by GO and KEGG analysis. Molecular docking was performed to analyze the interaction between ingredients and targets, cellular activity was evaluated by MTT assay, and RT-qPCR and western blot were used to evaluate the expressions of related genes. The results showed that 146 active therapeutic components can target hypertension-related genes, and we found that core genes were mainly involved in the metabolism of lipids, lipopolysaccharides, the inflammatory signaling pathway, and the oxidative stress pathway. In addition, there was high affinity between the components of NXT and targets of hypertension, where the former can increase cell viability and reduce the expressions of NOX4, MCP-1, BAX, TNF-α and IL-1ß. Moreover, NXT inhibited the expressions of IL-6 and Fis1, as well as increased the expression of MCL-1. These results revealed the active compounds, hypertension targets, signaling pathways, and molecular mechanisms of NXT for treating hypertension, offering references for the clinical application of NXT and the treatment of hypertension.

Effect of Vitamin D supplementation on blood pressure in hypertensive individuals with hypovitaminosis D: a systematic review and meta-analysis.

In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of Vitamin D supplementation on SBP and DBP levels in individuals with hypertension and hypovitaminosis D. PubMed, Scopus, Web of Science, and SciELO were systematically searched for relevant publications until January 2023. The review has been registered at PROSPERO (CRD42023400035). To compare the effects of vitamin D with placebo, the mean differences with 95% confidence intervals (95% CIs) were pooled based on the random-effects model. Subgroup analyses were performed to identify the source of heterogeneity, and assessment of study quality was conducted using the GRADE approach. Publication bias was evaluated using funnel plots and Egger's tests. In total, 14 randomized controlled trials (RCTs) were included in this systematic review, and 11 trials were selected for meta-analysis. The data showed that Vitamin D significantly decreased SBP levels; however, it did not affect DBP levels. In subgroup analysis, Vitamin D supplementation significantly decreased in SBP in studies involving individuals over 60 years of age, with a dose greater than 400 000 IU, duration greater than 8 weeks, frequency of weekly supplementation in studies conducted in Asia. In addition, subgroup analysis revealed a significant reduction in DBP in the weekly frequency subgroups and in the studies carried out in Asia. This meta-analysis indicated that Vitamin D significantly reduced the SBP in individuals with hypertension and hypovitaminosis D. Further, well designed trials are necessary to validate these results.