Acute Effects of Citrulline Malate Supplementation on Nocturnal Blood Pressure Dipping After Exercise in Hypertensive Patients: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Citrulline malate (CM), especially when used in conjunction with physical exercise, has demonstrated potential as a non-pharmacological adjunct in the management of hypertension. Nevertheless, its impact on nocturnal blood pressure dipping remains unexplored. OBJECTIVE: Evaluate the impact of a single dose of CM on nocturnal blood pressure dipping after exercise in hypertensive individuals. METHODS: In a double-blind, placebo-controlled, parallel-group clinical trial, twenty hypertensive adults (55 ± 16 years) were randomly assigned to either a CM (6 g) or placebo (6 g of corn starch) group (PLA). Resting blood pressure was measured after a 20-min period of comfortable seating in a calm environment. Both groups underwent 40 min of treadmill running/walking at an intensity of 60-70% of their reserve heart rate, 120 min after ingesting the substances. Ambulatory blood pressure monitoring was employed to measure blood pressure over 24 h. RESULTS: No significant differences in systolic blood pressure values were observed between the CM and PLA groups at rest, during wakefulness, sleep, or over a 24-h period. However, CM exhibited a significant reduction in diastolic blood pressure in several metrics: delta 24 h (-14 mmHg vs -6 mmHg, p = 0.047), delta wakefulness (-12 mmHg vs -4 mmHg, p = 0.024), percent delta 24 h (-16% vs -6%, p = 0.024), and percent delta wakefulness (-14% vs -4%, p = 0.013). No significant differences were found between CM and PLA in terms of systolic and diastolic nocturnal absolute reductions (-13 mmHg vs -12 mmHg, p = 0.808, and -13 mmHg vs -8 mmHg, p = 0.273, respectively) or nocturnal percentage decrease (-9.9% vs -9.4%, p = 0.844, and -15.3% vs -11.7%, p = 0.399, respectively). CONCLUSIONS: The study found no significant changes in the post-exercise nocturnal blood pressure dip following a single dose of CM supplementation. However, a notable reduction in diastolic blood pressure was observed during the waking period and over the average 24-h monitoring period. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ClinicalTrials.gov platform (NCT03378596).

Fructose-1,6-bisphosphate reverses hypotensive effect caused by L-kynurenine in Wistar male rats.

Hypotension is one of the main characteristics of the systemic inflammation, basically caused by endothelial dysfunction. Studies have shown that the amino acid L-kynurenine (KYN) causes vasodilation in mammals, leading to hypotensive shock. In hypotensive shock, when activated by the KYN, the voltage-gated potassium channel encoded by the family KCNQ (Kv7) gene can cause vasodilation. Fructose-1,6-bisphosphate (FBP) it is being considered in studies an anti-inflammatory, antioxidant, immunomodulator, and a modulator of some ion channels (Ca2+, Na+, and K+). We analyzed the effects of KYN and FBP on mean blood pressure (MBP), systolic and diastolic (DBP) blood pressure, and heart rate variability (HRV) in Wistar rats. Results demonstrated that the administration of KYN significant decreased MBP, DBP, and increased HRV. Importantly, the FBP treatment reversed the KYN effects on MBP, DBP, and HRV. Molecular Docking Simulations suggested that KYN and FBP present a very close estimated free energy of binding and the same position into structure of KCNQ4. Our results did demonstrate that FBP blunted the decrease in BP, provoked by KYN. Results raise new hypotheses for future and studies in the treatment of hypotension resulting from inflammation.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

INTRODUCTION: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. METHODS: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. ETHICS AND DISSEMINATION: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. TRIAL REGISTRATION: Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Systematic review and meta-analysis of second-generation sham-controlled randomized trials of renal denervation therapy for patients with hypertension

INTRODUCTION: Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. AIM: We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. METHODS: Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. RESULTS: Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. CONCLUSION: Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

Comparison of intensive treatment versus standard treatment in lowering blood pressure and its association with cognitive decline and dementia: a systematic review and meta-analysis

BACKGROUND: The ideal blood pressure target level for preventing cognitive decline or dementia in patients with systemic arterial hypertension (SAH) remains unclear. PURPOSE: This study aims to investigate whether intensive blood pressure reduction compared to standard treatment is associated with a reduced risk of cognitive decline or dementia in adults with SAH. METHODS: PubMed, Scopus and Cochrane databases were searched for randomized clinical trials (RCTs) comparing intensive treatment versus standard treatment for blood pressure reduction in patients with SAH. A random-effects model was used for analyzing the results, which were presented as relative risk (RR) with a 95% confidence interval (CI). Heterogeneity was examined using the I² statistic. Statistical analysis was performed using R software version 4.2.3. RESULTS: A total of 5 RCTs and 46,658 patients were included, of whom 23,726 (50,85%) underwent intensive therapy for SAH treatment. The mean age of participants ranged from 62.8 to 80.9 years in the intensive treatment group while it ranged from 63.3 to 80.3 years in the standard treatment group. Occurrence of dementia or probable dementia was significantly lower in the intensive treatment group (3.8% vs. 4,3%; RR 0.88; 95% CI: 0.80 - 0.96; p= 0.0049; I²=0%). Dementia or Cognitive decline (16.4% vs. 18.8%; RR 0.87; 95% CI 0.83 - 0.90; p < 0.000001; I²=0%), and cognitive decline (13.2% vs. 15.2%; RR 0.88; 95% CI 0.80 - 0.98; p= 0.014; I²=53%) also tended towards the intensive treatment group. Additionally, no significant association was found in mortality (6.4% vs. 7.3%; RR 0.87; 95% CI 0.75 - 1.02; p= 0.09; I²=28%) and serious adverse effects (34.4% vs. 35.5%; RR 0.99; 95% CI 0.92 - 1.06; p=0.73; I²=63%). CONCLUSION: Our study shows that intensive blood pressure treatment is associated with a fewer occurrence of dementia, probable dementia and cognitive decline in comparison to the standard blood pressure target.

Association between physical activity performed at different intensities and cardiovascular health in patients with peripheral artery disease: an observational study.

BACKGROUND: We examined the sedentary behavior and physical activity of 260 patients with peripheral artery disease. Women engaged in more light physical activity than men did. Light physical activity was associated with lower arterial stiffness in men only, while no significant associations were found between sedentary behavior, moderate-vigorous physical activity, and cardiovascular outcomes. BACKGROUND: ◼ Women with peripheral artery disease exhibited higher blood pressure and arterial stiffness than men. BACKGROUND: ◼ Low levels of physical activity, particularly moderate to vigorous activity, were observed in individuals with peripheral artery disease. OBJECTIVE: To analyze the association between the time spent in sedentary behavior and physical activity of different intensities with cardiovascular health in men and women with peripheral artery disease. METHODS: Two hundred and sixty patients with peripheral artery disease and claudication symptoms (65.7% men; 66±1 years; ankle brachial index 0.57±0.18) were evaluated. Physical activity and sedentary behavior were assessed using an accelerometer. Physical activity was classified into light and moderate-vigorous intensities. The cardiovascular outcomes included blood pressure (oscillometric method), cardiac autonomic modulation (heart rate variability), and arterial stiffness (pulse wave velocity). RESULTS: Women spent more time engaged in light physical activity than men (341±14 min/day versus 306±9 min/day; p=0.040, respectively). There was no significant difference in the time spent on sedentary behavior and moderate-vigorous physical activity. Women had a higher systolic blood pressure (p=0.025), higher augmentation index (p<0.001), and lower sympathovagal balance (p=0.047) than men. Pulse wave velocity was only negatively associated with light physical activity (ß= -4.66; 95%CI= -8.57; -0.76) in men. Light and moderate-vigorous physical activity and sedentary behavior were not associated with other cardiovascular outcomes. CONCLUSION: Higher levels of light physical activity were associated with lower arterial stiffness in men with peripheral artery disease.

Effects of cocoa consumption on cardiometabolic risk markers: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiometabolic diseases cover a spectrum of interrelated conditions linked to metabolic dysfunctions and/or cardiovascular disorders, including systemic arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. Cocoa is a rich source of dietary polyphenols and has been associated with cardiovascular health benefits. However, beneficial effects of cocoa consumption and appropriate quantities in decreasing cardiometabolic risk factors have yet to be established. Therefore, we will conduct a systematic review and meta-analysis to examine the effects of cocoa consumption on cardiometabolic risk markers (total cholesterol, HDL, LDL, triglycerides, blood glucose, glycated hemoglobin, waist circumference, abdominal circumference, body mass index, systolic blood pressure and diastolic blood pressure) in adults with or without established cardiovascular risk factors. METHODS: Our review will include all randomized controlled trials published in English, Portuguese and Spanish with no date of publication restrictions evaluating the effects of cocoa consumption on cardiometabolic risk markers selected from the databases MEDLINE (PubMed), LILACS, Cochrane, EMBASE, Web of Science and SciELO, and gray literature. Eligible studies must involve adults (age ≥18y), and the consumption of cocoa or dark chocolate (≥ 70% cocoa), include a control group and evaluate blood pressure, anthropometric measurements, and lipid or glycemic profiles. We will use risk-of-bias 2 (RoB2) tool to assess the risk of bias and the GRADE system to assess the strength of evidence. Statistical analyses will be performed using RStudio for Windows and R package meta. DISCUSSION: This meta-analysis will summarize existing evidence on the effects of cocoa consumption on cardiometabolic health in adults. Better understanding the effects of cocoa consumption on anthropometric measurements, blood pressure, and lipid and glycemic profiles can provide valuable insights for health professionals to improve dietary recommendations regarding appropriate quantities. TRIAL REGISTRATION: Systematic Review Registration: PROSPERO CRD42023484490.

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats.

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and ß-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

Dietary Inflammatory Index and Blood Pressure Levels in Mexican Adults.

BACKGROUND: The relationship between the dietary inflammatory index and blood pressure has been evaluated in European and American populations. This association remains unexplored in Mexico, where outcomes may differ due to the populace's ancestral heritage and its diverse dietary habits. METHODS: We used the Health Workers Cohort Study (2004 to 2018). DII intake was assessed using a food frequency questionnaire. Blood pressure was measured following standardized procedures and techniques. Fixed-effects linear regression and Cox regression models were utilized as the statistical approaches. RESULTS: In the first approach, we observed a positive association between changes in DII intake and changes in both systolic (SBP ß: 3.23, 95% CI 1.11, 5.34) and diastolic blood pressure (DBP ß: 1.01, 95% CI -0.43, 2.44). When stratified by hypertension, these associations were magnified in participants with hypertension (SBP ß: 6.26, 95% CI 2.63, 9.89; DBP ß: 1.64, 95% CI -0.73, 4.02). In the second approach, interactions between sex and age categories were explored. Participants in the highest DII category were associated with an increased risk of hypertension, particularly among young women (HR: 3.16, 95% CI 1.19, 8.43). CONCLUSIONS: Results suggest that a pro-inflammatory diet is associated with an increase in blood pressure over time among Mexican population.

Effectiveness of DASH Diet versus Other Diet Modalities in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Metabolic syndrome refers to the coexistence of several known cardiovascular risk factors, including insulin resistance, obesity, atherogenic dyslipidemia, and hypertension. These conditions are interrelated and share underlying mediators, mechanisms, and pathways. Improvement in dietary habits has been shown to improve metabolic parameters in patients undergoing treatment with different diets. METHODS: A systematic search in different databases was realized using the keywords "Metabolic syndrome", "X syndrome", "Dash dietary" and "Dash diet". Finally, six studies were included in this meta-analysis. RESULTS: All articles comparing the DASH diet vs. other diet modalities reported significant differences in favor of the DASH diet on Systolic blood pressure (SBP) (standardized mean difference [SMD] = -8.06, confidence interval [CI] = -9.89 to -7.32, and p < 0.00001), Diastolic blood pressure (SMD = -6.38, CI = -7.62 to -5.14, and p < 0.00001), Cholesterol HDL (SMD = 0.70, CI = 0.53 to 0.88, and p < 0.00001) and Cholesterol LDL (SMD = -1.29, CI = -1.73 to -0.85, and p < 0.00001) scales. CONCLUSIONS: The DASH diet has been shown to be beneficial in altered parameters in patients with MS, and the resulting improvements can significantly affect the daily health of these patients. We therefore recommend that professionals who manage these pathologies promote the use of the DASH diet for the management of specific symptoms.

Sarcoplasmic reticulum calcium ATPase (SERCA) proteolysis by matrix metalloproteinase-2 contributes to vascular dysfunction in early hypertension.

AIMS: Hypertension is associated with an increased activity of matrix metalloproteinase (MMP)-2 in the vasculature, which, in turn, proteolyzes extra- and intracellular proteins that lead to vascular dysfunction. The activity of sarcoplasmic reticulum calcium ATPase (SERCA) is decreased in the aortas of hypertensive rats. Increased activity of MMP-2 proteolyzed SERCA in rat heart during ischemia and reperfusion injury, thus impairing cardiac function. Therefore, we examined whether increased activity of MMP-2 in early hypertension contributes to proteolyze SERCA in the aortas, thus leading to maladaptive vascular remodeling and dysfunction. MAIN METHODS: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with doxycycline. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. After 7 days, aortas were collected for zymography assays, Western blot to SERCA, ATPase activity assay, vascular reactivity, Ki-67 immunofluorescence and hematoxylin/eosin stain. KEY FINDINGS: SBP was increased in 2K-1C rats and doxycycline did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and doxycycline decreased Ki-67. In 2K-1C rats, arterial relaxation to acetylcholine was impaired and doxycycline ameliorated it. SIGNIFICANCE: doxycycline reduced MMP-2 activity in aortas of 2K-1C rats and prevented proteolysis of SERCA and its dysfunction, thus ameliorating hypertension-induced vascular dysfunction.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown. Therefore, we investigated the role of sGC within the PVN in cardiovascular, autonomic, neuroendocrine, and local neuronal responses to acute restraint stress in rats. Bilateral microinjection of the selective sGC inhibitor ODQ (1 nmol/100 nl) into the PVN reduced both the increased arterial pressure and the drop in cutaneous tail temperature evoked by restraint stress, while the tachycardia was enhanced. Intra-PVN injection of ODQ did not alter the number of Fos-immunoreactive neurons in either the dorsal cap parvocellular (PaDC), ventromedial (PaV), medial parvocellular (PaMP), or lateral magnocelllular (PaLM) portions of the PVN following acute restraint stress. Local microinjection of ODQ into the PVN did not affect the restraint-induced increases in plasma corticosterone concentration. Taken together, these findings suggest that sGC-mediated signalling in the PVN plays a key role in acute stress-induced pressor responses and sympathetically mediated cutaneous vasoconstriction, whereas the tachycardiac response is inhibited. Absence of an effect of ODQ on corticosterone and PVN neuronal activation in and the PaV and PaMP suggests that PVN sGC is not involved in restraint-evoked hypothalamus-pituitary-adrenal (HPA) axis activation and further indicates that autonomic and neuroendocrine responses are dissociable at the level of the PVN.

Mas receptor blockade impairs exercise-induced cardiac hypertrophy.

Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.

Comparison of arterial stiffness index predictors in perimenopausal and postmenopausal women.

The present cross-sectional study aimed to compare climacteric symptoms and arterial stiffness indices between perimenopausal and postmenopausal women. The study sample comprised 70 healthy female participants, including 27 perimenopausal (49.8 ± 3.8 years) and 43 postmenopausal (55.7 ± 4 years) individuals. Validated methods were used to assess physical activity level, quality of life, climacteric symptoms, and anthropometric data. Arterial stiffness parameters were measured using Mobil-O-Graph. Pulse wave velocity (PWV) had a higher mean in the postmenopausal group than in the perimenopause group [8.04 m/s (SD 0.79) vs 7.01 m/s (SD 0.78), p < .001). PWV was strongly correlated with peripheral (r = 0.619) and central (r = 0.632) Systolic Blood Pressure (SBP) in postmenopausal group and an even stronger correlation was observed in perimenopausal group (r = 0.779 pSBP and 0.782 cSBP). BMI was a risk predictor in the perimenopausal group contributing positively to increase Pulse Pressure Amplification (PPA) (0.458, p < .05). In postmenopausal women, heart rate (HR) was a stronger predictor for central SBP, cardiac output, and total vascular resistance, whereas perimenopausal women HR influenced central diastolic blood pressure and PPA. Vascular changes initiating during perimenopause may contribute to the development of cardiovascular pathologies in the postmenopausal period. Further research with larger, representative samples is warranted to corroborate these findings.

OXGR1-Dependent (Pro)Renin Receptor Upregulation in Collecting Ducts of the Clipped Kidney Contributes to Na+ Balance in Goldblatt Hypertensive Mice.

The two-kidney, one-clip (2K1C) Goldblatt rodent model elicits a reduction in renal blood flow (RBF) in the clipped kidney (CK). The reduced RBF and oxygen bio-ability causes the accumulation of the tricarboxylic cycle intermediary, α-ketoglutarate, which activates the oxoglutarate receptor-1 (OXGR1). In the kidney, OXGR1 is abundantly expressed in intercalated cells (ICs) of the collecting duct (CD), thus contributing to sodium transport and electrolyte balance. The (pro)renin receptor (PRR), a member of the renin-angiotensin system (RAS), is a key regulator of sodium reabsorption and blood pressure (BP) that is expressed in ICs. The PRR is upregulated in 2K1C rats. Here, we tested the hypothesis that chronic reduction in RBF in the CK leads to OXGR1-dependent PRR upregulation in the CD and alters sodium balance and BP in 2K1C mice. To determine the role of OXGR1 in regulating the PRR in the CDs during renovascular hypertension, we performed 2K1C Goldblatt surgery (clip = 0.13 mm internal gap, 14 days) in two groups of male mice: (1) mice treated with Montelukast (OXGR1 antagonist; 5 mg/Kg/day); (2) OXGR1-/- knockout mice. Wild-type and sham-operated mice were used as controls. After 14 days, 2K1C mice showed increased systolic BP (SBP) (108 ± 11 vs. control 82 ± 5 mmHg, p < 0.01) and a lower natriuretic response after the saline challenge test. The CK group showed upregulation of erythropoietin, augmented α-ketoglutarate, and increased PRR expression in the renal medulla. The CK of OXGR1 knockout mice and mice subjected to the OXGR1 antagonist elicited impaired PRR upregulation, attenuated SBP, and better natriuretic responses. In 2K1C mice, the effect of reduced RBF on the OXGR1-dependent PRR upregulation in the CK may contribute to the anti-natriuretic and increased SBP responses.

Assessment of fluid responsiveness using pulse pressure variation, stroke volume variation, plethysmographic variability index, central venous pressure, and inferior vena cava variation in patients undergoing mechanical ventilation: a systematic review and meta-analysis.

IMPORTANCE: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes. OBJECTIVE: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients. REGISTRATION: The protocol was registered at PROSPERO: CRD42019146781. INFORMATION SOURCES AND SEARCH: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023. STUDY SELECTION AND DATA COLLECTION: Prospective and intervention studies were selected. STATISTICAL ANALYSIS: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed. RESULTS: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89). CONCLUSIONS: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

Effects of 12 weeks of functional training vs. Muay Thai on cardiac autonomic modulation and hemodynamic parameters in older adults: a randomized clinical trial.

BACKGROUND: The elevated blood pressure (BP) and lower cardiac autonomic modulation (CAM) are associated with higher morbidity mortality risk among older adults. Although exercise is an important intervention for cardiovascular promotion, it is unclear whether combat sports training could benefit cardiovascular outcomes as much as autonomic in this population. This study compared the effects of 12 weeks of Muay Thai (MT) training against functional training (FT) on CAM and hemodynamic parameters in older adults. METHODS: The sample consisted of 50 older adults (41 women; 66.0 ± 5.3 years old), who were equaly randomized into FT (n = 25) and MT (n = 25) intervention groups. CAM was measured by 30-min rest heart rate variability. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and resting heart rate (RHR) were measured using an automatic oscillometric device. Pulse pressure (PP) and the double product (DP) were also calculated. The interventions were carried out three times a week, with 60-min length per session, during 12 consecutive weeks. The intensity of the interventions was measured using the subjective perception of exertion scale and by accelerometer. Two-factor repeated measures analysis of covariance was used for groups comparison, considering intervention group and body mass as factors. The 95% confidence interval of the difference (95%CIdif) was also calculated and the effect size was measured using partial eta squared (η2p). RESULTS: CAM indices did not show significant changes across moments and intervention groups. In hemodynamic parameters, only in DBP was there an effect of the moment (F1,39 = 8.206; P = 0.007; η2p = 0.174, large) and interaction effect between group*moment (F1,39 = 7.950; P = 0.008; η2p = 0.169, large). Specifically, the MT group at the post-training moment showed lower DBP (P = 0.010; 95%CIdif = -13.3; -1.89) in relation to the FT group. Furthermore, the MT group showed a decrease in DBP during training (P = 0.002; 95%CIdif = -10.3; -2.6). Also, an increase in training intensity was also found over the 12 weeks in FT, with no difference between the groups. CONCLUSION: After 12 weeks of MT practice there was a reduction in DBP compared to FT in older adults. TRIAL REGISTRATION: NCT03919968 Registration date: 01/02/2019.

The Association of Blood Pressure Defined by the 2017 ACC/AHA Guidelines and Cardiovascular Disease Risk for Middle-Aged and Elderly People in China: A Cohort Study. / A Associação de Pressão Arterial Definida pelas Diretrizes ACC/AHA de 2017 e Risco de Doença Cardiovascular para Pessoas de Meia-Idade e Idosas na China: Um Estudo de Coorte.

BACKGROUND: Cardiovascular disease (CVD) is a series of diseases affecting the heart or blood vessels. OBJECTIVES: To assess the relationship between blood pressure (BP) levels defined by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline and CVD/atherosclerotic cardiovascular disease (ASCVD) risk for middle-aged and elderly people in China. METHODS: A total of 6,644 middle-aged and elderly people from the China Health and Retirement Longitudinal Study (CHARLS) were finally included. According to the 2017 ACC/AHA guideline, all subjects were divided into four groups: normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension. The outcome of this study was considered as the risk of CVD and ASCVD. Univariate and multivariate COX regression models were adopted to examine the relationship of the 2017 ACC/AHA BP classification with the risk of CVD. Univariate and multivariate logistic regression models were used to investigate the association between BP levels and ASCVD risk. Subgroup analyses based on age, gender, and use of antihypertensive drugs were performed. P<0.05 was accepted as statistically significant. RESULTS: After adjusting all covariates, compared to middle-aged and elderly patients with normal BP, we found that patients with stage 1/2 hypertension were associated with a higher risk of CVD, separately. Simultaneously, we also observed a positive association between individuals with elevated BP, stage 1 hypertension, stage 2 hypertension, and higher ASCVD risk in the fully adjusted model. The result of subgroup analyses implied that the relationship between stage 1/2 hypertension and CVD/ high ASCVD was robust in different ages and genders, and participants without using antihypertensive drugs. CONCLUSION: BP classification under the 2017 ACC/AHA BP guidelines may apply to the Chinese population.

Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

BACKGROUND: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. OBJECTIVES: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N=1,433 Puerto Rico PROTECT study participants. METHODS: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. RESULTS: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture odds ratio(OR)=1.57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB ß=0.78 (95% CI: 0.17, 1.38) and adjusted P-PB ß=0.85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ß=-0.57; 95% CI: -1.09, -0.05). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. CONCLUSIONS: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.