INTRODUCTION:Cancer patients often experience increased activity of the Sympathetic Nervous System (SNS). A dysregulation in the stress-related catecholamines secretion, including norepinephrine (NE) and epinephrine (EPI), has been associated with tumor progression and worse clinical and psychological outcomes. However, the systemic secretion profile of NE and EPI and their predictors in patients with oral cancer have been poorly investigated. PATIENTS AND METHODS:The present study investigated the association of plasma NE and EPI levels in 168 patients with Oral Squamous Cell Carcinoma (OSCC) with demographic, clinicopathological, biobehavioral and psychological variables. Catecholamine levels in patients with oral cancer were compared to hormone levels in patients with oral leukoplakia and healthy individuals. Plasma NE and EPI levels were measured by High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED). Psychological mood states and emotional symptoms were assessed by the Brunel Mood Scale (BRUMS). RESULTS:Systemic NE concentrations were significantly higher in patients with OSCC compared to patients with oral leukoplakia (p < 0.001) and healthy volunteers (p = 0.003). Patients with OSCC also displayed increased plasma EPI levels, but this result did not reach significance after adjusting for covariates (p = 0.098) and was influenced by the tobacco consumption (p = 0.018). Multivariate analyzes identified the mood descriptors "anger" and "alert" as predictive variables for increased NE plasma levels in OSCC patients (β = 0.260, SE = 0.117, .028 and β = 0.151, SE = 0.073, p = 0.004, respectively). No variable was associated with EPI plasma levels in OSCC patients. CONCLUSION:The results reveal that patients with oral cancer display increased systemic concentrations of stress-related catecholamines, and that higher levels of norepinephrine are associated with the emotional symptoms of anger and alertness.

The increase in combat sports practice and the creation of weight divisions for fairer competitions led to dehydration practice as a strategy of inclusion in inferior divisions. However, this technique can damage kidney and heart functions due to alterations in blood volume. This study evaluated the acute effects of weight loss through dehydration on the kidney function of Mixed Martial Arts and Muay Thai fighters. The sample was composed of 30 athletes of both Mixed Martial Arts (n = 15) and Muay Thai (n = 15) fighters. Both groups went through two protocols for collecting data about the athlete's profile, vital signs, and urinary and blood samples in three different moments: before weigh-in, official weigh-in day, and fight day. The athletes' profiles and the dehydration methods employed were found to be consistent with those reported in the literature. The participants lost weight 1 month before the fight and had alterations that developed into glycosuria, leukocyturia, and proteinuria noted on both official weigh-in and combat days. Proteinuria and high creatinine depuration suggest acute kidney damage with an increase in filtration rate due to dehydration. As shown, there is a necessity for proper athlete orientation regarding dehydration and possible damage to the body's physiological integrity and sport performance, and developing a guide on more appropriate weight control protocols that do not put athletes' health at risk should be established and publicized.

BACKGROUND:Hypertrophic scar and keloids are skin conditions strongly influenced by an imbalance of the renin-angiotensin-aldosterone system (RAAS). These disorders affect mainly African, Asian, and Spanish populations, and current treatments may not yield adequate results. This study aimed to demonstrate the RAAS modulation capacity of high-molecular-weight hyaluronic acid (HMWHA) in dermal fibroblasts. METHODS:Renin, Angiotensin-converting enzyme (ACE), and Angiotensin-converting enzyme 2 (ACE2) activities were assessed fluorometrically after treating cells with ACE inhibitors (captopril or enalapril) or HMWHA (linear or BDDE cross-linked, a biomaterial widely used as a human dermal filler), administered either alone or in combination. RESULTS:After 120 min treatment, the greatest reductions in renin and ACE activities were obtained with CHA-S (53.76 ± 15.51 nmol/min/mg) and HA-S (0.051 ± 0.013 nmol/min/mg), respectively. ACE2 activity, however, had its largest increase with Ena (75.49 ± 11.49 nmol/min/mg). The ACE2/ACE ratio, for the same treatment period, was greatly increased for both Ena and HA-S (923.1 ± 178.7; 1209 ± 287.0, respectively). CONCLUSION:This study demonstrated that HMWHA promotes the protective axis of RAAS, with known anti-inflammatory and anti-fibrotic effects, by enhancing ACE2 activity and reducing ACE activity, opening perspectives for therapeutic approaches targeting cicatricial alterations and inflammatory and fibrotic dermal diseases.

Angiotensin-converting enzymes (ACE and ACE2) are key components of the renin-angiotensin-aldosterone system (RAAS) and are present in the gastrointestinal tract and intestinal content, preserving their catalytic activity, and may interact with the gut microbiota. The present study aimed to determine the origin of fecal ACE and ACE2 activity. Fecal pellets from germ-free, ACE and ACE2 knockout (KO) mice, and from the corresponding controls were analyzed using fluorimetric enzyme activity assays. ACE activity was assessed using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates; ACE2 activity was assessed using Mca-APK (Dnp), with and without the ACE2 inhibitor MLN-4760. Germ-free mice showed increased fecal ACE and ACE2 activity compared to controls. ACE2-KO mice lacked fecal ACE2 activity, whereas ACE activity was unaffected. In ACE-KO mice, fecal ACE activity was reduced, but not abolished, while ACE2 activity remained similar to controls. In ACE C- and N-domain KO mice, ACE activity was similar to controls, and inhibition with captopril completely abolished fecal ACE activity using Hippuryl-His-Leu, but not Z-Phe-His-Leu, in those animals. These findings indicate that fecal ACE and ACE2 activity results from combined intestinal shedding and microbiota-related mechanisms, supporting a modulatory role of the gut environment on luminal RAAS activity.

To investigate the involvement of metalloproteinases (MMPs) in the context of endurance training and their interactions with renin-angiotensin signalling (RAS) in stress-induced pathophysiological responses. Trained rats were submitted to 8-weeks of endurance treadmill training with chronic mild stress (CMS), TS rats, and without CMS (T). Non-trained rats (NTS and NT groups) were submitted to identical procedures except for training. NTS and TS groups were submitted to a CMS protocol for 3 weeks. Elevated corticosterone levels indicate an initial triggering factor that mediates the downstream intracellular signalling networks related to the MMPs and RAS activation after CMS. Endurance training confers cardioprotection against the stress response by lowering the Ang 3-7 levels, whereas increased activity of MMPs was observed in TS rats. Chronic stress disrupts the cardiac function, MMPs, and RAS activation by increasing the cardiac activity of the MMP-2 activity and Ang 1-9 levels with concomitant reduction of cardiac and blood levels of Ang 1-7. Stress also reduced circulating levels of Ang 1-9 and Ang 1-5, Ang 1-7 metabolites, along with increased Ang III (2-8). Aerobic endurance training is a potential exercise-based strategy that counteracts the stress-related disturbances in the MMPs and RAS signalling pathways.

Background:Activation of the intrarenal renin-angiotensin system (RAS) is a key mechanism driving sodium retention and hypertension. In the distal nephron, locally generated angiotensin II (Ang II) promotes Na+ reabsorption through coordinated regulation of the epithelial Na+ channel (ENaC) in principal cells and electroneutral NaCl transport mediated by pendrin and the Na+-dependent Cl-/HCO3- exchanger (NDCBE) in intercalated cells. Emerging evidence identifies α-ketoglutarate as an intrarenal paracrine signal acting through oxoglutarate receptor 1 (OXGR1), which is highly expressed in collecting duct intercalated cells. We hypothesized that OXGR1 is required to couple intrarenal RAS activation with collecting duct Na+ transport and blood pressure regulation during Ang II-dependent hypertension. Methods:mice were subjected to chronic Ang II infusion (400 ng·min-1·kg-1, 14 days) using two approaches: pharmacological OXGR1 blockade with montelukast (3.5 μg ·min-1·kg-1) and global OXGR1 genetic deletion (OXGR1-/-). Blood pressure, Na+ balance, and the renal abundance of pendrin, NDCBE and αENaC were assessed. Intrarenal RAS activity was evaluated by measuring Ang I (renin activity), Ang II, ACE activity and (pro)renin receptor (PRR). Results:Ang II infusion increased blood pressure, promoted antinatriuresis, and elevated intrarenal Ang II, ACE activity, PRR, pendrin, and αENaC protein abundance. In contrast, both montelukast-treated wild type and OXGR1-/- mice infused with Ang II displayed attenuated hypertensive responses, reduced Na+ retention, and failed to increase intrarenal Ang II, pendrin, or αENaC abundance. Conclusion:These findings identify OXGR1 as a critical regulator linking intrarenal RAS activation to distal nephron Na+ transport and suggest that OXGR1-dependent signaling contributes to sodium retention and the development of Ang II-induced hypertension.

Introduction:Amino acids are fundamental in several metabolic processes, and their levels can reflect metabolism impairments that contribute to obesity and related diseases. Our objective was to identify a urinary amino acid fingerprint in obese and overweight children in prepuberty and to correlate this profile with cardiometabolic alterations. Methods:The study included 110 children, boys and girls aged 9-10 years, they were classified according to their BMI-for-age (Body Mass Index for age) into three groups: normal weight (NW) (n = 45), overweight (OW) (n = 21), and obese (OB) (n = 44). The 12-h urine samples were analyzed by LC-MS/MS to quantify 47 amino acids using the Amino Acids Analysis Kit (Zivak®, Turkey), values were corrected by creatinine concentration. Anthropometric measurements, cardiovascular parameters, and biochemical profiles were assessed following standard protocols. Results:When compared to NW, anthropometric measures, systolic and diastolic blood pressure, and serum uric acid levels were progressively elevated in the OW and OB groups. The OB group was characterized by elevated alpha-aminoadipic acid, asparagine, cystathionine, 1-methyl-histidine, serine, tryptophan, phenylalanine, and tyrosine. In contrast, the OW group presented the most expressive levels of glutamine, alpha-diaminopimelic, and sarcosine. Discussion:Our findings indicate that obese and overweight children exhibit a particular urinary amino acid fingerprint which is similar to that reported in studies with plasma. The altered amino acids, particularly tyrosine, are frequently associated with impairments in glucose homeostasis, insulin resistance, and diabetes mellitus type 2. Potential mechanisms for increasing the levels of these amino acids in excess of weight may include enhanced protein degradation and impaired oxidative metabolism.

Introduction: Chronic stress adversely impacts the cardiovascular system, partly by inducing gut dysbiosis, contributing to cardiovascular diseases. Probiotics, known for their antioxidant properties, may modulate pathways like SIRT1 activation, improving endothelial function and reducing oxidative stress. Objective: This study aimed to test whether probiotic treatment reduces oxidative stress, modulates SIRT1 expression and positively influences blood pressure in chronic stress. Methods: Male Wistar rats (n=8/group) were assigned to Control (C), Stress (S), Control+Probiotic (CP), and Stress+Probiotic (SP) groups. Probiotics ( Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri, 1 billion CFU/probiotics, Terapêutica Farmácia de Manipulação, Brazil) were administered for 8 weeks. Chronic mild and unpredictable stress (CMUS - protocol #6533240621) was applied during weeks 3–5. Blood pressure was measured by plethysmography, and biochemical analyses were conducted using commercial kits. Results: The CUMS protocol induced stress, increasing corticosterone levels (S: 206.4 ± 150 vs. C: 60.8 ± 34 ng/mL, p<0.05), mitigated by probiotics (SP: 59.2 ± 75.7 ng/mL, p<0.05). Stress increased insulin levels (S: 68.5 ± 18 vs. C: 41 ± 18.5 pg/mL, p<0.05; SP: 79.2 ± 25 vs. CP: 41 ± 12 pg/mL, p<0.05), CK levels (S: 17.02 ± 6.59 vs. C: 7.29 ± 3.28; SP: 9.88 ± 1.99 U/L), and SIRT1 expression (S: 1.02 ± 0.2 vs. C: 0.64 ± 0.13 2- ΔΔCT ), effects reversed by probiotics, except by SIRT1. Probiotics also increased antioxidant enzyme activity (SOD1: SP: 57.41 ± 1.32 vs. S: 52.48 ± 1.27%, p<0.05; Catalase: SP: 23603 ± 5868 vs. S: 5045 ± 193.7 mIU/mL, p<0.05) and altered gut microbiota, increasing Lactobacillus (SP: 24.6% vs. S: 18.41%) and Prevotellaceae_NK3B31_group (SP: 12.71% vs. S: 10.82%). The biochemical changes observed were accompanied by functional alterations, with probiotic reducing mean blood pressure (SP:83±9 vs. S:123±8 mmHg). Conclusion: Probiotics positively impacted oxidative stress markers and regulated blood pressure in rats under chronic stress, effects that appear to be not mediated by SIRT1 modulation. Additionally, probiotics altered gut microbiota composition. Collectively, our findings suggest that probiotics may serve as a complementary strategy for managing cardiovascular risk associated with chronic stress. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2021/05331-1 and 2017/17027-0]. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: The impact of COVID-19 on pregnancy remains incompletely understood. The presence of the primary SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), in the placenta suggests a potential vulnerability of this organ. Beyond the risk of vertical transmission, ACE2 may be depleted during viral entry, disrupting its biological functions. During pregnancy, ACE2 plays a critical role in placentation and hemodynamic adaptations by regulating the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). Hypothesis: We hypothesize that SARS-CoV-2 interaction with ACE2 may disrupt placentation and impairs uteroplacental circulation, contributing to clinical complications such as preeclampsia and intrauterine growth restriction. Objectives: To compare the expression of angiotensin (Ang) II, Ang 1-7, and ACE2 in placentas from SARS-CoV-2-infected pregnant women and uninfected controls. METHODS: Women admitted for labor at the Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife, Brazil, were tested for COVID-19 using nasopharyngeal RT-PCR. From March 2020 to September 2021, we recruited 160 COVID-19-negative controls and 126 COVID-19-positive participants. Obstetric and clinical data, as well as formalin-fixed paraffin-embedded placental biopsies, were collected. Participants were further stratified by COVID-19 severity. Histopathological analysis focused on identifying signs of malperfusion and inflammation were conducted. A Tissue Microarray block was created to analyze Ang II, Ang 1-7, and ACE2 expression through immunohistochemistry. Results: COVID-19 severity was associated with adverse pregnancy outcomes, including low birth weight, preterm birth, APGAR scores below 7, and fetal death. Placentas were lighter, and the placental-to-fetal weight ratio was higher in affected pregnancies. Ang II expression showed a trend towards higher levels in the COVID-19-positive group (105.3 ± 2 vs. 101.5 ± 3, p = 0.06), while ACE2 expression (107.6 ± 12 vs. 75.9 ± 14, p = 0.04) and the Ang II to Ang 1-7 ratio (0.99 ± 0.1 vs. 0.93 ± 0.1, p = 0.03) were significantly elevated. ACE2 expression correlated with lower birth weight and APGAR scores, while both ACE2 and the Ang II to Ang 1-7 ratio were linked to an increased placental-to-fetal weight ratio, indicative of fetal growth restriction. Conclusion: Our findings demonstrate a dysregulation of RAS in COVID-19-affected placentas, characterized by an elevated Ang II to Ang 1-7 ratio and increased ACE2 expression. The higher Ang II to Ang 1-7 ratio reflects a shift towards the vasoconstrictive and pro-inflammatory axis of RAS. Upregulation of ACE2 may increase susceptibility to placental SARS-CoV-2 infection. Although vertical transmission is rare, viral replication can compromise placental function, contributing to the heightened prevalence of adverse maternal-fetal outcomes in COVID-19 pregnancies. Further studies will assess ACE, SARS-CoV-2, inflammatory markers, and vascular density to deepen our understanding. Supported by Sao Paulo Research Foundation (FAPESP) proc:. 2022/02452-5 and 2017/17027-0. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The purpose of this paper is to describe the development of a low-cost insulin infusion pump software simulator. The simulator was built using Java programming language and replicates the interface and functions of a real low-cost insulin infusion pump currently under development. Potential users participated in a remote session, and assessment was conducted using a standard usability scale (SUS). With a sample size of 34 participants possessing different levels of knowledge regarding diabetes and infusion pumps, the mean SUS score obtained was 67.43. While the insulin infusion pump is a specialised device and its system may not be immediately familiar to all users, the results suggest that usability can improve with appropriate training and clinical support. Employing a simulation model during the development of the physical prototype may provide advantages for system design, safety, and effectiveness in health care technology delivery.

Introduction: Systemic arterial hypertension (SAH) is a multifactorial common public health problem in the elderly Brazilian population. Communities such as the quilombolas, remnants of enslaved peoples, face even more difficulties when compared to urban populations, with evidence in the literature of SAH even in adolescents. Hypothesis: Are there clinical and impeccable differences in hypertension between the quilombola population and urban populations? Method: A total sample of 1127 elderly people (235 quilombolas, 318 São Luís, nearest capital, 574 São Paulo, capital with the highest HDI in the country) were included. Systolic and diastolic blood pressure, ACE gene insertion/deletion polymorphism associated with susceptibility to SAH, BMI, and fasting blood glucose were evaluated and classified in the three populations in the quilombolas and the food consumption of the quilombolas. Results: The classification of hypertension and the distribution of the ACE polymorphism were different between the elderly quilombolas and the two urban populations (which did not differ between them), incidence of hypertension: 81.52% quilombolas, 26.27% São Luís and 27.18% São Paulo) in the ACE polymorphism the elderly quilombolas had a higher incidence of allele I, protective regarding the incidence of hypertension. Regarding BMI, the elderly quilombolas had more underweight individuals and less overweight when compared to the two urban populations. There were no statistical differences in the presence of altered fasting glucose among the 3 populations. Regarding food consumption, the elderly quilombolas had a high consumption of flours and low consumption of vegetables and legumes. Conclusion: It seems that the high incidence of hypertension in elderly quilombolas is more associated with environmental than endogenous factors. We present alarming parameters regarding the incidence of hypertension in the elderly quilombola population, and therefore, public policies need to turn their attention to this vulnerable population.

[This corrects the article DOI: 10.3389/fphys.2025.1524939.].

There is scientific evidence that supports the association between aerobic exercise capacity and the risk of developing complex metabolic diseases. The factors that determine aerobic capacity can be categorized into two groups: intrinsic and extrinsic components. While exercise capacity is influenced by both the intrinsic fitness levels of an organism and the extrinsic factors that emerge during training, physiological adaptations to exercise training can differ significantly among individuals. The interplay between intrinsic and acquired exercise capacities represents an obstacle to recognizing the exact mechanisms connecting aerobic exercise capacity and human health. Despite robust clinical associations between disease and a sedentary state or condition, the precise causative links between aerobic exercise capacity and disease susceptibility are yet to be fully uncovered. To provide clues into the intricacies of poor aerobic metabolism in an exercise-resistant phenotype, over two decades ago a novel rat model system was developed through two-way artificial selection and raised the question of whether large genetic differences in training responsiveness would bring about aberrant systemic disorders and closely regulate the risk factors in health and diseases. Genetically heterogeneous outbred (N/NIH) rats were used as a founder population to develop contrasting animal models of high versus low intrinsic running capacity (HCR vs. LCR) and high versus low responsiveness to endurance training (HRT vs. LRT). The underlying hypothesis was that variation in capacity for energy transfer is the central mechanistic determinant of the divide between complex disease and health. The use of the outbred, genetically heterogeneous rat models for exercise capacity aims to capture the genetic complexity of complex diseases and mimic the diversity of exercise traits among humans. Accumulating evidence indicates that epigenetic markers may facilitate the transmission of effects from exercise and diet to subsequent generations, implying that both exercise and diet have transgenerational effects on health and fitness. The process of selective breeding based on the acquired change in maximal running distance achieved during a treadmill-running tests before and after 8 weeks of training generated rat models of high response to training (HRT) and low response to training (LRT). In an untrained state, both LRT and HRT rats exhibit comparable levels of exercise capacity and show no major differences in cardiorespiratory fitness (maximal oxygen consumption, VO2max). However, after training, the HRT rats demonstrate significant improvements in running distance, VO2max, as well as other classic markers of cardiorespiratory fitness. The LRT rats, on the other hand, show no gain in running distance or VO2max upon completing the same training regime. The purpose of this article is to provide an overview of studies using LRT and HRT models with a focus on differences in neuromuscular adaptations. This review also summarizes the involved molecular and cellular signaling pathways underlying skeletal muscle adaptations in LRT models in comparison to the HRT model, which responds positively to endurance training. The LRT-related adverse effects in neuromuscular responses seem to be primarily driven by: (i) impaired glucose tolerance or impaired insulin sensitivity, (ii) increased extracellular matrix (ECM) remodeling, (iii) loss of type I muscle fibers, (iv) mitochondrial dysfunction, and (v) intricate cellular signaling orchestrated by TGF-ß1-JNK and TNF-α-MAPK pathways. Alternatively, the HRT model demonstrates improved neurovascular and muscle remodeling responses and increased central nervous system excitability, which might reflect an inherent protective mechanism to stress events.

Physiological control of blood pressure (BP) and extracellular fluid volume is mediated by the action of the renin-angiotensin system (RAS). The presence of RAS components throughout the nephron has been widely discussed. The (pro)renin receptor (PRR) is a member of the RAS widely expressed in the body of humans and rodents. In the kidney, PRR is expressed in mesangial cells, renal vasculature, and tubules of the proximal and distal nephron. Binding of the PRR to renin and prorenin promotes angiotensin (Ang) I-mediated sodium (Na+) reabsorption via the epithelial sodium channel (ENaC). The Goldblatt 2-kidney 1-clip (2K1C) is a model of experimental renovascular hypertension that displays activation of systemic and intrarenal RAS. We use the 2K1C hypertension mouse model for 7 days to evaluate the role of the PRR on renal αENaC expression, Na+ reabsorption, and BP using pharmacological systemic blockade of the PRR with PRO20 peptide. Mice undergoing or not to 2K1C surgery (0.13 mm clip internal gap) were chronically infused with PRO20 and compared to sham (control) mice to assess changes in systolic BP (SBP) and diastolic BP (DBP), intrarenal angiotensin-converting enzyme (ACE) activity, Ang II, and renal αENaC expression and natriuretic responses after a saline challenge. Renal artery obstruction increased SBP and DBP, intrarenal ACE activity, Ang II levels, Na+ retention, and αENaC expression in both kidneys. PRO20 prevented the increases in SBP, DBP, attenuated Na+ retention, and blunted intrarenal Ang II and αENaC levels in non-clipped kidneys of 2K1C mice. Chronic infusion of the PRR for 7 days prevents hypertensive responses in part due to impaired αENaC upregulation and intrarenal Ang II formation in the early phase of the development of renovascular hypertension in 2K1C Goldblatt mice.

Introduction: The affinity of SARS-CoV-2 for the Angiotensin Converting Enzyme 2 (ACE2), component of the Renin-Angiotensin System (RAS), is responsible for the COVID-19 virus internalization, and the ACE and ACE2 genes polymorphisms may contribute for the disease outcome. Objective: To correlate the I/D ACE and the G8790A ACE2 polymorphisms and their enzymatic activity to the virus susceptibility and the disease's clinical severity. Methods: 408 patients from Alfa Hospital, Recife – PE, were assessed. ACE activity was measured by fluorometry and the real time PCR technique was used to assess ACE's DD, ID, and II polymorphisms. Results: 71.9% of COVID-19 affected patients needed hospitalization, with 56.8% being male ranging from 40 to 59 years old. In the positive group, there were more patients with blood hypertension (80.6% vs 19.4%), diabetes (88.2% vs 11.8%), and obesity (87.5% vs 12.5%). ACE activity was higher in positive patients (46.5 vs 43.5 nmol/mL/min), with greater prevalence of the DD genotype, 85.6% of frequency between negatives and positives. When it comes to DD genotype, ACE activity was higher (48.5 nmol/mL/min). In patients with blood hypertension, ID genotype was more frequent than the DD one. Conclusion: The interaction of genetic and risk factors may lead to different COVID-19 symptomatology. The scientific literature states that ACE polymorphism may contribute for the development of blood hypertension, as the DD genotype being the susceptible one for developing cardiovascular complications by the higher concentration of Angiotensin II converted from Angiotensin I by ACE, increasing the hypertensive effects in relation to the anti-hypertensive ones of Angiotensin 1-7. The positive group showed more incidence of blood hypertension, diabetes and obesity, as well as higher frequency of the DD genotype, which is already established in literature to lead to blood hypertension due to increased ACE activity. From the observed in these results, it is suggested a correlation between ACE polymorphism and the factors that may aggravate COVID-19

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1–7) [Ang-(1–7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1–7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

Background: The two-kidney, one-clip (2K1C) Goldblatt model elicits a reduction of renal blood flow (RBF) in the clipped kidney (CK). The reduced RBF and oxygen bio ability causes the accumulation of the intermediary of the tricarboxylic cycle, α-ketoglutarate, which activates the oxoglutarate receptor-1 (OXGR1). In the kidney, the OXGR1 is abundantly expressed in intercalated cells (IC) of the collecting duct (CD), which may contribute to Na+ transport and electrolyte balance. The (pro)renin receptor (PRR), a member of the renin-angiotensin-aldosterone system is a key regulator of Na+ reabsorption, and blood pressure (BP) and is also expressed in IC. PRR is upregulated in 2K1C. Here, we tested the hypothesis that reduction of RBF in the CK leads to OXGR1-dependent PRR upregulation in the CD and alterations of Na+ balance and BP in 2K1C mice. Methods: To determine the role of OXGR1 in regulating PRR in the CDs during renovascular hypertension, we used 2K1C Goldblatt surgery (clip= 0.13 mm internal gap) in two groups of male mice: 1) Oxgr1-/- knockout (n=6) mice; and 2) mice treated with Montelukast (OXGR1 antagonist; 5 mg/Kg/day, n=6). WT and sham-operated mice were used as controls. Results: 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 showed augmented levels of α-ketoglutarate, erythropoietin mRNA levels, PRR (mRNA and protein abundances) in the renal medulla. Non-CK showed PRR upregulation in the CDs. However, the CK of Oxgr1-/- knockout mice, and from those subjected to OXGR1 antagonism, elicited impaired PRR upregulation, attenuated SBP (Oxgr1-/- 2K1C: 90 ± 8 mmHg, p=non-significant vs. control; Montelukast 2K1C: 95 ± 3 mmHg, p<0.05 vs. control) and better natriuretic responses. Conclusion: 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.