STATEMENT OF PROBLEM:The effects of different denture stomatitis (DS) management strategies on oral health-related quality of life (OHRQoL) and salivary flow (SF) in complete denture wearers remain unclear. PURPOSE:The purpose of this double-blind, parallel-group randomized clinical trial was to compare the effects of nystatin therapy and sodium hypochlorite denture hygiene on OHRQoL, salivary flow (SF), and DS severity in complete denture wearers. MATERIAL AND METHODS:A total of 50 complete denture wearers with DS were allocated to 2 groups: nystatin mouth rinse (GN) or a sodium hypochlorite (GSH0.25%)-based denture hygiene protocol. OHRQoL, SF, and DS severity were assessed at baseline and at 15 and 45 days, and data were analyzed using generalized estimating equations (α=.05). RESULTS:Forty-seven participants completed the study. Significant improvements over time were observed in OHRQoL overall and domains related to masticatory function, social disability, and psychological discomfort (P≤.001), regardless of treatment, with no treatment-by-time interactions. SF remained stable over time, with no significant effects of treatment, time, or interaction (P>.05). DS severity decreased significantly over time (P<.001), with no significant differences between groups or interaction effects (P>.05). CONCLUSIONS:Both therapies were associated with improved OHRQoL in complete denture wearers with DS. These improvements occurred alongside reductions in denture stomatitis severity, while salivary flow remained stable, suggesting a multifactorial process involving clinical and behavioral factors.

Enhanced cholinergic signaling is associated with cardioprotection, with cardiomyocyte Gi activation via M2 muscarinic receptors proposed as a contributing mechanism. To test this therapeutic strategy, we engineered Myh6-Cre/hM4Di mice to selectively activate Gi signaling in cardiomyocytes (CM-Gi+) using DREADD technology. Gi pathway engagement was temporally controlled through clozapine-N-oxide (CNO) administration, and we evaluated its impact in a model of adrenergic-induced cardiomyopathy. In vitro, CNO reduced myocyte shortening in Myh6-Cre/hM4Di cardiomyocytes. It also suppressed isoproterenol (ISO)-induced contractility enhancement and phosphorylation of PKA target motifs, consistent with Gi activation. In vivo, a 7-day ISO regimen induced cardiac hypertrophy, inflammation, and expression of fibrosis markers, all prevented by CNO-driven CM-Gi+ signaling. This intervention also preserved cardiomyocyte viability under ISO challenge in vitro and in vivo, underscoring its cytoprotective effects. To evaluate the therapeutic potential of this cell-targeted approach at a more advanced stage of injury, CNO treatment was initiated on day 4 of a 7-day ISO protocol, when cell death and inflammation are prominent. Echocardiographic, histological and flow cytometry analyses demonstrated that delayed CM-Gi+ stimulation restored cardiac function and prevented macrophage accumulation. Contractility assessments confirmed normalization of myocyte function in ISO-treated mice, supporting the concept of cardiomyocyte recovery. Mechanistically, these beneficial effects were associated with reduced cardiac infiltration of CCR2+ monocytes, key drivers of adverse remodeling. Our findings identify cardiomyocyte-specific Gi activation as a cytoprotective strategy that promotes myocardial repair under sustained adrenergic stress. This work lays the foundation for precision cell-targeted therapies aimed at modulating cholinergic/Gi signaling in the injured heart.

IntroductionHeart rate fragmentation (HRF) quantifies rapid beat-to-beat irregularity in cardiac intervals and has emerged as a predictor of adverse cardiovascular outcomes. While standard heart rate variability (HRV) indices primarily reflect autonomic modulation, HRF has been proposed to capture intrinsic sinoatrial node dynamics largely independent of autonomic influences. However, the extent to which HRF is shaped by cardiac autonomic balance in healthy individuals remains unclear. We examined whether HRF responds to controlled physiological shifts in autonomic modulation and investigated its relationship with established HRV indices. MethodsTwenty healthy adults (29 ± 4 years) underwent two complementary autonomic challenges: a graded head-up tilt test to progressively increase sympathetic drive and attenuate vagal cardiac modulation, and controlled breathing at 0.1 Hz to selectively enhance cardiac parasympathetic activity in a slow frequency band. HRF indices were quantified along with standard time- and frequency-domain HRV parameters and symbolic dynamic analysis. Associations between HRF and HRV indices were assessed using Spearman’s rank correlation coefficients. ResultsGraded tilt produced a progressive reduction in HRF indices that closely paralleled decreases in vagally mediated HRV parameters. HRF indices, particularly the percentage of inflection points (PIP), showed strong correlations with the 2UV symbolic pattern (r = 0.74). Controlled breathing enhanced parasympathetic modulation and elicited a shift of respiratory oscillations from high- to low-frequency spectral bands. All variations corresponding to high frequencies (HF, 2UV%, PIP, and other indices related to more fragmented rhythms) decreased in favor of an increase in low-frequency variations (LF/HF, 0V%, 2LV%). DiscussionRather than providing information purely about cardiovascular autonomic control, these findings indicate that, in healthy subjects, both HRV and HRF indices are strongly influenced by cardiorespiratory coupling. Collectively, these results provide the first evidence that HRF in healthy individuals is significantly influenced by autonomic activity, especially parasympathetic modulation. These findings challenge the prevailing view of HRF as a purely intrinsic, autonomic-independent marker, indicating that it is also influenced by the respiratory frequency range. Taken together, these observations indicate that HRF reflects autonomic mechanisms under physiological conditions. Whether this relationship is preserved or altered under pathological conditions remains to be established and warrants investigation in future studies.

Neuroimmune communication is essential for regulating inflammation and maintaining cardiovascular homeostasis, but the role of sensory pathways in this process is poorly understood. Arterial baroreceptors are typically defined as mechanoreceptors essential for arterial pressure homeostasis and have been associated with modulation of the immune response. However, their role in sensing systemic inflammation remains unknown. Here, we establish the molecular profile of the rat aortic depressor nerve (ADN) as an immune-competent tissue and investigate its response to lipopolysaccharide (LPS)-induced endotoxemia. Using analysis of gene expression, total protein quantification, and immunofluorescence assay, we demonstrate that the ADN, from male Sprague–Dawley rats (7–8 weeks old), constitutively expresses key components for innate immune signalling, including Toll-like receptor 4 (TLR4), MyD88, and phosphorylated NF-κB, indicating a state of constant immunological vigilance. LPS administration induced an inflammatory response within the ADN, upregulating gene expression of NF-κB, interleukin-6, and type I interleukin 1 receptor, and it also increased the ADN electrical activity. Notably, the increase in nerve firing occurred while the animals were experiencing systemic hypotension and also during the diastolic phase, indicating that this response is not from the mechanosensory reflex. Furthermore, we characterized the progression of this immune response in the nodose ganglion and aortic arch, identifying a coordinated neuroimmune sensory axis. These findings reposition arterial baroreceptors from purely mechanoreceptors to integrative immunosensors that actively detect and respond to systemic inflammation. This novel neuroimmune circuit represents a critical link between inflammation and cardiovascular system, offering a novel therapeutic target for treating cardiovascular and inflammatory conditions.

Introduction: Testosterone is utilized in gender transition protocols for transmasculine individuals. It has pro-hypertrophic effects in the myocardium and enhances glycolytic pathways in cardiomyocytes that modulate cardiac remodeling. T cells are crucial for immune responses and contribute to cardiovascular disease. Effector CD4+ T cells drive adverse cardiac remodeling. Pyruvate kinase (PK) regulates glycolysis, but its PKM2 isoform is mostly inactive in monomeric/dimeric forms, requiring allosteric activation for full function. In the present study, we tested the hypothesis that testosterone, impairs cardiac function by increasing the glycolytic metabolism in CD4 + T cells in an experimental model of gender-affirming hormone therapy (testo-GAHT). Methods: Female C57/BL6 wild type (WT) mice, female Rag1 knockout (Rag1 -/- ) mice, Rag1 -/- that received WT CD4 + T cells (Rag1 -/- ¬CD4 + ), and female mice that do not express the enzyme Pkm2 in CD4 + T cells (CD4 Cre Pkm2 fl/fl ) were treated with testosterone cypionate (48 mg.kg -1 .wk -1 ) or vehicle (peanut oil), for 8 weeks. Results: Echocardiogram analysis showed that testo-GAHT in WT females promoted cardiac hypertrophy characterized by increased intraventricular septum thickness (IVSd), and decreased left ventricular internal diameter (LVIDd); and functional changes - characterized by increased E/A wave ratio as an indicator of diastolic dysfunction, along with elevated ejection fraction (EF%) and fractional shortening (FS%) as measures of contractility, and heart rate (BPM); and decreased left ventricular stroke volume (LV Vols). Testo-GAHT (for 24 weeks) also increased blood pressure in WT females. Flow cytometry analysis of ex vivo hearts showed increased CD31 + ICAM + cells and decreased CD45 + CD11b + in testo-GAHT WT mice. In the mediastinal lymph nodes (mLN), the number of T cells remained unchanged, although effector CD4 + CD44 hi CD62L lo cells increased. In the spleen, there was a decrease in CD4+ T cells, but like the mLN, the frequency of effector cells increased, while the frequency of CD4 + RORgt + cells decreased. The cardiovascular changes induced by testo were not observed in Rag1 -/- females. Transfer of CD4 + cells to Rag -/- mice (Rag1 -/- ¬CD4 + ) restored the cardiovascular effects (IVSd, EF%, FS%, BPM and CO) of testo-GAHT. Ex vivo, by extracellular flux assays (Seahorse XF96 analyzer), testo increased glycolysis, glycolytic capacity, and non-glycolytic acidification, assessed by the extracellular acidification rate (ECAR) assay, and increased gene expression of solute carrier family 2 (GLUT1), lactate dehydrogenase A (Ldha) and Pkm2, suggesting an increased metabolism in these cells. CD4 Cre Pkm2 fl/fl females on testo-GAHT showed preserved EF%, BPM and CO, parameters elevated in littermate controls under hormonal treatment. In vitro, testo-treated CD4+ T cells preincubated with a pharmacological inhibitor and activator of Pkm2 tetramerization exhibited reduced differentiation of activated CD4+ T cells toward Th17 profile, analyzed by flow cytometry. Conclusion: Despite the adverse effects on cardiac function and blood pressure, testo provides significant immunomodulatory advantages. The glycolytic pathway plays a crucial role in these benefits, modulating CD4 T cell activity and reducing the inflammatory response, revealing important targets that can be used as markers of cardiovascular risk in transmasculine individuals undergoing testo-GAHT. Approval by the Ethics Committee: CEUA-FMRP/USP (1026/2021) and IACUC-Tufts University (B2023-25). Financial support: FAPESP, CAPES, CNPq and NIH. 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.

G-protein coupled receptors (GPCRs) are key modulators of cardiac function. Hyperactive Gs and Gq pathways are linked to cardiac disease, while Gi activation via ACh binding to muscarinic type 2 receptors promotes cardioprotection. We aimed to selectively activate Gi signaling in cardiomyocytes (CMs) to assess its therapeutic potential in a adrenergic overload-induced cardiac damage model. To selectively activate Gi in CMs, we crossed the R26-LSL-Gi-hMD4i model with Myh6-CRE, creating a Myh6-Cre/hM4Di mice, in which upon N-Oxide-Clozapine (CNO) stimulation activates Gi selectively in cardiomyocytes (CMs). Male and female mice (8 weeks old) were subjected to: Protocol 1: CMs were isolated, electrically stimulated to contract, and treated with Isoproterenol (ISO 50nmol/L), ACh, or CNO (100nmol/L). Protocol 2: Myh6-Cre/hM4Di mice were treated in vivo with ISO (25 mg/kg/day) with or without CNO (0.5 mg/kg/day) for 7 days. Mice were sacrificed on day 8. The data was derived from at least three independent experiments. Normality was assessed using the Shapiro-Wilk test. For normal data, an unpaired Student's t-test or one-way ANOVA with Tukey's post hoc test was used. For non-normal data, the Mann-Whitney U or Kruskal-Wallis test was applied, followed by the Games-Howell post hoc test when appropriate. A significance threshold of p < 0.05 was applied. To confirm the activation of the Gi pathway in CMs the cells were exposed to CNO or ACh (positive control for Gi), and contraction was recorded. Myh6-Cre/hM4Di cells exhibited reduced shortening area after CNO stimulation, while no effect was observed in cells from Myh6-CRE or hM4Di littermate mice. Next, we investigated whether Gi activation in CMs could attenuate the ISO-induced tissue injury in vivo (protocol 2). CNO treatment of Myh6-Cre/hM4Di mice prevented ISO-induced pathological cardiac remodeling, including hypertrophy, inflammation and fibrosis. To explore whether Gi activation could reverse pre-existing cardiac injury, we started CNO injection on day 4 of a 7-day ISO treatment, at a stage when cell death and inflammation were already occurring. We found that late CNO treatment reversed ISO-induced cardiac and CM hypertrophy. Flow cytometry analyses showed a reduction in inflammatory cells, which directly impacted the fibrotic and functional cardiac outcomes. This was evidenced by fewer myofibroblasts, reduced collagen I and III transcripts, and improved echocardiographic parameters, confirming the efficacy of late CNO treatment in cardiac recovery. These results demonstrate, for the first time that targeted Gi activation in CMs protects against adrenergic overload-induced cardiac injury, highlighting CM-Gi's role in cardiac repair. CNPq, CAPES e FAPEMIG 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.

AIM:To evaluate the effect of carotid sinus nerve stimulation (CSNS) in the progression of cardiorenal syndrome type 1 (CRS1), 3 days after acute myocardial infarction (AMI). METHODS:Male rats were divided into four groups. CSNS was applied daily for 10 min over 3 days. Cardiac, renal, and inflammatory parameters characterized the CRS1 and the electroceutical effects of CSNS. RESULTS:CSNS reduced the ischemic zone compared to the AMI group not exposed to CSNS (32.7% ± 2.2% vs. 8.0% ± 1.8%). Heart rate (bpm) was increased in the AMI group, showing 440 ± 7.6 at 48 h and 428 ± 1.0 at 60 h post-AMI. Additionally, arterial pressure (mmHg) was increased in the AMI group at 48 h, as follows: mean: 98 ± 1.7, diastolic: 89 ± 2.1, and systolic: 122 ± 5.3. In contrast, the CSNS + AMI group showed significant reductions of these parameters: mean: 79 ± 2.0, diastolic, 66 ± 1.7, and systolic: 99 ± 2.7. Renal injury was confirmed by increased apoptosis in the AMI group. A significant increase in TNF-α was observed in both heart and kidneys (pg/mg of tissue) in the AMI group and reduced IL-6 and IL-1β levels in the CSNS + AMI group, indicating an attenuation of the inflammatory responses by CSNS. CONCLUSIONS:This study demonstrates early cardiac and renal dysfunction in CRS1 following AMI, associated with elevated inflammatory markers (TNF-α, IL-6, and IL-1β) and renal apoptosis. Therefore, CSNS appears to be a promising electroceutical approach for CRS1. Besides, on the basis of previous studies from our laboratory, CSNS involves stimulation of the baroreflex, activating the parasympathetic and inhibiting the sympathetic nervous system.

IntroductionObstructive sleep apnea (OSA) is a prevalent sleep disorder with a high rate of undiagnosed patients, primarily due to the complexity of its diagnosis made by polysomnography (PSG). Considering the severe comorbidities associated with OSA, especially in the cardiovascular system, the development of early screening tools for this disease is imperative. Heart rate variability (HRV) is a simple and non-invasive approach used as a probe to evaluate cardiac autonomic modulation, with a variety of newly developed indices lacking studies with OSA patients.ObjectivesWe aimed to evaluate numerous HRV indices, derived from linear but mainly nonlinear indices, combined or not with oxygen saturation indices, for detecting the presence and severity of OSA using machine learning models.MethodsECG waveforms were collected from 291 PSG recordings to calculate 34 HRV indices. Minimum oxygen saturation value during sleep (SatMin), the percentage of total sleep time the patient spent with oxygen saturation below 90% (T90), and patient anthropometric data were also considered as inputs to the models. The Apnea-Hypopnea Index (AHI) was used to categorize into severity classes of OSA (normal, mild, moderate, severe) to train multiclass or binary (normal-to-mild and moderate-to-severe) classification models, using the Random Forest (RF) algorithm. Since the OSA severity groups were unbalanced, we used the Synthetic Minority Over-sampling Technique (SMOTE) to oversample the minority classes.ResultsMulticlass models achieved a mean area under the ROC curve (AUROC) of 0.92 and 0.86 in classifying normal individuals and severe OSA patients, respectively, when using all attributes. When the groups were dichotomized into normal-to-mild OSA vs. moderate-to-severe OSA, an AUROC of 0.83 was obtained. As revealed by RF, the importance of features indicates that all feature modalities (HRV, SpO2, and anthropometric variables) contribute to the top 10 ranks.ConclusionThe present study demonstrates the feasibility of using classification models to detect the presence and severity of OSA using these indices. Our findings have the potential to contribute to the development of rapid screening tools aimed at assisting individuals affected by this condition, to expedite diagnosis and initiate timely treatment.

This systematic review explores the relationship between the oral microbiome in edentulous patients and cardiovascular diseases (CVD). A search was conducted across databases PubMed, Scopus, Web of Science, Embase, and gray literature sources. The review followed PRISMA and AMSTAR guidelines. After removing duplicates, the articles were evaluated by titles and abstracts, and 21 were selected for full-text review, with 9 ultimately included in the final analysis. Oral dysbiosis, linked to systemic conditions like obesity, diabetes, and CVD, is common in inflammatory oral diseases such as periodontitis and denture stomatitis, disrupting original oral microbiota. This imbalance may lead to transient bacteremia and systemic inflammation, contributing to CVD development. Tooth loss reduces salivary microbiome diversity, and denture use in CVD patients is linked to decreased life expectancy compared to dentate individuals. The findings suggest tooth loss, denture use, and oral microbiota dysbiosis are unconventional risk factors for CVD progression.

Objective: To evaluate the influence of edentulism, smoking, microbiota, and oral rehabilitation on the cytokine profile in healthy and hypertensive edentulous individuals using complete dentures. Design: This case-control study was divided into four groups: normotensives (control group - NH), controlled hypertensives (case group 1 - CH), unreported hypertensives (case group 2 - UnrH), and uncontrolled hypertensives (case group 3 - UncH). The participants were characterized by sociodemographic data, clinical and behavioral information, and systolic and diastolic blood pressure. The microbial load of Candida spp., Staphylococcus spp., enterobacteria, and mutans streptococci was evaluated by quantifying colony-forming unit. Salivary flow and salivary cytokines (IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-17) were quantified in unstimulated saliva by mL per minute and by flow cytometry, respectively. Results: Eighty patients (66 +/- 7.2 years) were evaluated. The duration of edentulism was positively associated with systolic blood pressure (p = 0.012). Patients with non-functional denture rehabilitation, those with only upper complete dentures, showed significantly higher systolic blood pressure (p = 0.024) and levels of IL-2 (p = 0.024), predominantly in UncH. The colony-forming unit of mutans streptococci on the denture was higher in UncH and showed a negative association with smoking habit, and this had a positive association with salivary cytokines (IL-4, IL-2, IL-17, IFN-gamma) and CVD. Conclusions: The interplay between edentulism, smoking, and oral rehabilitation significantly impacts the cytokine profile, particularly in hypertensive conditions. Smoking habits modulated microbiota and interleukin profile, especially in cardiovascular patients. Moreover, non-functional dentures are associated with uncontrolled hypertension, marked by increased systolic blood pressure and IL-2.

With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension.

Objectives: Cardiovascular diseases are the leading global cause of mortality. Approximately 20 to 31% of acute myocardial infarction (AMI) cases progress to renal dysfunction, indicating concurrent cardiac and renal alterations, characterizing Cardiorenal Syndrome Type 1 (CS1). Therefore, this study evaluates the CS1 onset and progression three days after AMI by examining renal and cardiac function and their inflammatory responses. The study hypothesizes that inflammatory mediators are a key component contributing significantly to the onset and progression of CS1 pathophysiology. Methods: Male Sprague-Dawley rats (250-300g) were divided into AMI-SHAM (undergoing sham surgery for AMI) and AMI (left coronary artery ligation) groups. Samples were collected three days post-AMI from blood, urine, heart, and renal tissues. Assessments included osmolality (plasma and urine), creatinine (plasma and urine), glomerular filtration rate (GFR), and tissue cytokine levels. Left ventricular end-diastolic pressure (LVEDP) represented cardiac function. Results are presented as mean ± standard error. Results: LVEDP measurements (mmHg) demonstrated similar results from SHAM (5.89 ± 0.61, n=14) and AMI groups (6.38 ± 0.43, n=6). Tumor Necrosis Factor-Alpha (TNF-α) levels (pg/mg of tissue) from the heart [SHAM (2.74 ± 0.50, n=10) vs AMI (5.05 ± 0.83, n=8)] and renal tissue [SHAM (2.37 ± 0.69, n=7) vs AMI (5.53 ± 0.41, n=5)] were significantly different (p<0.05) concerning their respective groups. Of note, molecular biochemical analyses revealed similar results. Plasma Osmolality (kgH2O): SHAM (310.8 ± 5, n=13) vs AMI (310.4 ± 2.57, n=10); Urinary Osmolality: SHAM (1653 ± 140, n=14) vs AMI (2054 ± 166.9, n=9); Plasma Creatinine (mg/dL): SHAM (0.35 ± 0.21, n=14) vs AMI (0.39 ± 0.25, n=10); Urinary Creatinine: SHAM (118.9 ± 12.35, n=14) vs AMI (126.5 ± 18.90, n=10). GFR (mL/min/100g) was also similar: SHAM (1.22 ± 0.18, n=14) vs AMI (1.22 ± 0.12, n=9). Conclusions: The study shows that the increase of TNF-α is contributing to the onset and progression of the pathophysiology of CS1, in line with the original hypothesis. On the other hand, because the three-day post-surgery timeframe addressed the primary mechanisms triggering the CS1, it seems that the functional impairment of the heart and kidneys was not manifest yet. Support or Funding Information: FAPESP Process 2020/06043-7. CNPq Processes 306994/21-6 and 423999/21-4; FAEPA; CAPES/PROEX. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BACKGROUND Tooth loss has been established as a correlate with an increased risk of cardiovascular disease (CVD) and hypertension. However, the influence of complete denture usage on hypertension remains inadequately explored in scientific literature.METHODS This case-control study evaluated the microbial load of the biofilm of dentures and the palate, salivary levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17) and Salivary Flow (SF) of healthy (CG), controlled hypertensives (G1), underreported hypertensives (G2) and uncontrolled hypertensives (G3). The sample was characterized by sociodemographic data, clinical information, systolic (SBP), and Diastolic Blood Pressure (DBP). The microbial load of Candida spp., Staphylococcus spp., enterobacteria, and mutans group streptococci was evaluated by quantifying colony-forming unit (CFU), SF of unstimulated saliva by mL per minute, and salivary cytokines by flow cytometry.RESULTS 80 patients were evaluated (66±7.2 years). The time of edentulism was longer in G3 and positively associated with SBP. The CFU of mutans group streptococci on the denture was higher in G3 and showed a negative association with smoking habit, and this had a positive association with salivary cytokines (IL-4, IL-2, IL-17, IFN-γ), diabetes, and CVD. Patients in group G3, who only use upper dentures, had significantly higher SBP (p=0.024) and levels of IL-2 (p=0.024).CONCLUSIONS Time of edentulism may play a role in hypertension. Smoking habits modulated microbiota and interleukins, especially in diabetic and CVD patients. Furthermore, non-functional dentures had an association with hypertensive patients not controlled by medication, reflected in an increase in SBP and IL-2.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementSupported by grant FAPESP 2020/06043-7 and scholarships from the Coordination for the Improvement of Higher Education Personnel (CAPES, code: 001).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Human Research Ethics Committee of the Ribeirão Preto School of Dentistry, University of São Paulo (FORP/USP) (CAAE: 93712418.1.0000.5419).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data referenced in this manuscript may be made available upon request from the authors.

Background: We have previously demonstrated that electrical stimulation of the carotid sinus nerve (CSN) protects the development of periodontitis. In the current study, we evaluated whether periodontitis accelerates the onset of hypertension in spontaneously hypertensive rats (SHR); and whether electrical stimulation of the CSN would delay the onset of hypertension. Methods: Three-week old SHR were implanted with electrodes around the CSN for electrical stimulation for 13 days. Bilateral ligation of the first molar and oral administration of Porphyromonas gingivalis induced periodontitis. The femoral artery of the SHR was cannulated, and 24 h later, in a conscious state, the blood pressure was recorded. Results: Five-week old sham SHR (subjects without electrical stimulation of the CSN) did not demonstrate hypertension. However, when the SHR were submitted to periodontitis they exhibited hypertension at 5 weeks of age. Nevertheless, the stimulation of the CSN prevented the onset of hypertension. Periodontitis promoted alveolar bone loss in SHR; but, electrical stimulation of the CSN prevented this undesirable outcome following the exposure to periodontitis. Conclusion: Periodontitis accelerated the onset of hypertension in SHR; while the electrical stimulation of the CSN delayed the onset of hypertension.

Objectives: Arterial hypertension and the inflammatory process are pathophysiologically associated. Of note, it is well understood that periodontitis is an inflammatory morbidity, epidemiologically related to cardiovascular mortality, particularly with the risk of developing arterial hypertension. Considering that in Spontaneously Hypertensive Rats (SHR) the elevation of arterial pressure starts from the 7th week of age, this study aimed to evaluate whether periodontitis accelerates the onset of arterial hypertension, for instance, in 5-week-old SHR. Methods: Induction of periodontitis was started in 3-week-old SHR and maintained for 2 weeks through the ligation of the left first molar with a silk suture, followed by the Porphyromonas gingivalis (strain W83) administration, p.o., 3 times a week. The femoral artery of 5-week-old SHR was cannulated, and 24 hours later, with the animals awakened, the systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures were recorded. Results: 5-week-old control SHR (SHAM) did not have installed arterial hypertension, while SHR with periodontitis (PER) exhibited a higher arterial pressure when compared to the SHAM group (SAP PER: 150±4 vs. SAP SHAM: 124±3 mmHg, n=8, p≤0.001; DAP PER: 103±5 vs. DAP SHAM: 85±5 mmHg, n=8, p≤0.05; MAP PER: 119±4 vs. MAP SHAM 98±4 mmHg n=8, p ≤0.01). Conclusion: The differences observed in the pressure values between the groups studied demonstrate that periodontitis accelerates the development of hypertension in SHR. Funding Sources: Fundação de Amparo à Pesquisa do Estados de São Paulo - FAPESP, Process 2021/08622-7 and 2020/06043-7. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Process 306994/2021-6 and 423999/2021-4. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Objective: Neuroimmune interactions have been extensively explored to find new therapeutic targets for inflammatory diseases. We postulated that baroreceptors (essential for arterial pressure control) might be susceptible to systemic inflammation. Thus, the present study investigated the effect of early-stage systemic inflammation on aortic baroreceptor afferent activity. Hypothesis: Aortic depressor nerve activity is increased during systemic inflammation. Methods: Anesthetized (urethane; 1 g/kg; i.p.) male Sprague-Dawley rats (7-8 weeks old) were used, and lipopolysaccharide (LPS; 1.5 mg/kg; i.v.) injected to induce systemic inflammation. The femoral artery and vein were cannulated for pulsatile arterial pressure recording and LPS administration, respectively. Following 30 min since injections of either saline (control; n = 10) or LPS (n = 16), pulsatile arterial pressure and aortic depressor nerve activity were recorded. Nerve activity recordings were rectified and integrated on a time basis. Body temperature was measured via rectal thermometer. The results are presented as mean ± standard error of the mean. Results: Compared to saline-treated rats, there was an increase in aortic depressor nerve activity (LPS: 1.04 ± 0.02 vs saline: 0.98 ± 0.01 a.u.; p = 0.007); this was accompanied by increases in diastolic arterial pressure (LPS: 83 ± 2 vs saline: 73 ± 4 mmHg; p = 0.031), mean arterial pressure (LPS: 102 ± 3 vs saline: 91 ± 4 mmHg; p = 0.035) but not systolic pressure (LPS: 140 ± 6 vs saline: 122 ± 6 mmHg; p = 0.057; strong trend) or heart rate (LPS: 425 ± 11 bpm vs saline: 393 ± 14; p = 0.085). Importantly, in the LPS-injected rats, a reduction in body temperature was noted compared to saline-treated rats (LPS: 36.7 ± 0.1 vs saline: 37.2 ± 0.2°C; p = 0.005), an indicative of systemic inflammation. Conclusions: Since the diastolic and mean arterial pressures increased after LPS administration, it remains unclear whether the elevated aortic depressor nerve activity reflects this increased pressure or results from the inflammatory mediated sensitization. However, our preliminary data support the notion that aortic baroreceptor afferents participate in the neuroimmune communication response in the early stages of inflammation. Funding sources: FAPESP (protocols #2021/03764-8 and #2021/05554-0). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Heart Rate Variability (HRV) and arterial pressure (AP) variability and their responses to head-up tilt test (HUTT) were investigated in Post-COVID-19 syndrome (PCS) patients reporting tachycardia and/or postural hypotension. Besides tachycardia, PCS patients also showed attenuation of the following HRV parameters: RMSSD [square root of the mean of the sum of the squares of differences between adjacent normal-to-normal (NN) intervals] from statistical measures; the power of RR (beat-to-beat interval) spectra at HF (high frequency) from the linear method spectral analysis; occurrence of 2UV (two unlike variation) pattern of RR from the nonlinear method symbolic analysis; and the new family of statistics named sample entropy, when compared to control subjects. Basal AP and LF (low frequency) power of systolic AP were similar between PCS patients and control subjects, while 0 V (zero variation) patterns of AP from the nonlinear method symbolic analysis were exacerbated in PCS patients. Despite tachycardia and a decrease in RMSSD, no parameter of HRV changed during HUTT in PCS patients compared to control subjects. PCS patients reassessed after 6 months showed higher HF power of RR spectra and a higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0 V patterns of AP, while the HUTT elicited HR (heart rate) and AP responses identical to control subjects. The HRV and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients. In contrast, the lack of responses of HRV and AP variability indices during HUTT indicates a marked impairment of autonomic control. Of note, the reassessment of PCS patients showed that the noxious effect of COVID-19 on autonomic control tended to fade over time.

Background: We demonstrated that electrical stimulation of thecarotid sinus nerve (CSN) has a protective effect on the development ofPeriodontitis (PER). However, whether PER accelerates the onset ofhypertension in SHR is unknown. If this is true, it could be expected that theactivation of the CSN would retard the onset of hypertension. Objective: To evaluate whether PER accelerates the onset of hypertension inSHR; and whether the electrical stimulation of the CSN in SHR would delay theonset of this outcome. Methods: Three weeks old male SHRs were implanted with electrodes aroundthe CSN for daily electrical stimulation (3V; 1 ms; 30Hz; 10 minutes per day, fortwo weeks), combined with bilateral ligation of the lower first molar with a silksuture for PER induction. Besides, PER induction was combined with theadministration, p.o., of Porphyromonas gingivalis (strain W83) injected threetimes a week. The femoral artery of a five-week-old SHR was cannulated, and 24hours later, with the animals awakened, the systolic (SAP), diastolic (DAP), andmean (MAP) arterial pressure were recorded. Control SHR (SHAM) was notexposed to PER. Results: Five weeks old control SHR (SHAM) did not have installed arterialhypertension. However, when the SHR were submitted to PER, they alreadyexhibited a higher arterial pressure at five weeks, when compared to the SHAMgroup (SAP PER 150±4 vs. SHAM 124±3 mmHg, n=8, p≤0.001; DAP PER 103±5 vs. SHAM 85±5 mmHg, n=8, p≤0.05; MAP PER 119±4 vs. SHAM 98±4 mmHg,n=8, p ≤0.01). Nevertheless, the stimulation of the CSN prevented this increasein blood pressure in the five weeks old SHR submitted to PER (PAS SHR PERstim. 130±4 vs. SHAM 124±3 mmHg; PAD SHR PER stim. 84±3 vs. SHAM 85±5mmHg; PAM SHR PER stim. 99±4 vs. SHAM 98±4 mmHg, n=8, p>0, 05). Conclusion: PER accelerated the onset of arterial hypertension in SHR withinfive weeks. However, the activation of the baroreceptor and chemoreceptor reflexes through the electrical stimulation of the CSN in SHR exposed to PERdelayed the onset of arterial hypertension.

Background: The literature shows that partially or entirely edentulous patients can have an increased risk of cardiovascular diseases, particularly hypertension and stroke. However, edentulous patients wearing complete dentures present Denture Stomatitis (DS) very frequently, associated with deleterious cardiovascular effects, mainly arterial hypertension. Objective: This study evaluated blood pressure, C-reactive protein (CRP), body mass index (BMI), and lipid profiles of completely edentulous DS-positive patients at baseline, and after 15 and 45 days of treatment. Methods: The treatment protocol consists of brushing the palate with a soft brush and water, denture brushing with a denture-specific brush and mild soap, and oral, topical application of nystatin 100,000 IU. The degree of DS was diagnosed by two calibrated and blinded researchers using the modified Newton classification. Three measurements were performed at 5-minute intervals recording the systolic and diastolic blood pressure. The ELISA assessed the CRP (mg/L) of blood samples. The Friedman test and Dunn's post-test evaluated blood pressure (mmHg), BMI (kg/m 2 ), and lipid profile (mg/dL) data. ANOVA and Tukey's post-test was applied for CRP using the software SPSS 25.0 (p<0.05). Results: Twenty-five participants were included, with a mean age of 68±6.4 years.DS degree decreased over time (p<0.001), significantly decreasing after 15 days and intermediate values after 45 days. Systolic blood pressure showed a trend for reduction at 15 days (147.9±17.3 vs. 141.7±19.0 mmHg; p=0.058) and a significant decrease after 45 days (147.9±17.3 vs. 140.5±14.1 mmHg; p=0.017), while diastolic blood pressure was similar over time (88±13.3, 87±10.5 and 86±9.8 mmHg). The treatment did not significantly affect the CRP (1.3±0.9; 1.3±0.1; 1.1±0.1 mg/L; p=0.824), BMI (30.1±6; 30.3±6; 30.2±6 kg/m 2 ; p=0.391), and lipid profile (Total cholesterol: 187.3±39; 185.2±40; 185.3±33 mg/dl; p=0.416, HDL: 48.9±11.5; 49.0±9.8; 47.4±11.0 mg/dL; p=0.217). Conclusion: The applied treatment of DS reduced the patients' DS degree and systolic arterial pressure.

Although rapid oscillations of the heart rate (HR) are attributed to vagal modulation of the heart, a pattern of ultra-rapid HR variation has been named heart rate fragmentation (HRF). It is a recently proposed approach to evaluate sino-atrial instability characterized by the presence of numerous inflections points in a series of successive values of cardiac intervals. HRF is increased in aging and coronary diseases. Hypertension markedly alters HRV indices and might affect HRF as well. This study aimed to investigate the HRF in renovascular hypertension in rats. Wistar rats were anesthetized, and hypertension was surgically induced by partial constriction of the left renal artery with a silver clip with a 0.2 mm gap. In one kidney one clip (1K1C) hypertension model, the contralateral kidney was removed. In two kidneys one clip (2K1C) model, the contralateral kidney was kept intact. Sham-operated control rats underwent to same surgical procedures without receiving the clip around the renal artery. After 45 days (2K1C) or 60 days (1K1C), animals were instrumented with a catheter into the femoral artery, and on the following day, their arterial pressure (AP) was directly recorded without the effect of anesthesia. For HRF analysis, pulse interval (PI) series were generated and transformed into a sequence of symbols “-1,” “0,” or “1” when the difference between successive PI values (transitions) was negative, zero, or positive, respectively. Following, sequences of 4 consecutive symbols were classified according to the number of transitions. The total percentage of inflection points (PIP) and the percentage of sequences with zero (W0), one (W1), two (W2), or three (W3) inflection points were quantified. As expected, the arterial pressure increased in both groups of hypertension rats compared to control counterparts. All HRF indices were found similar in 1K1C hypertensive rats compared to their control counterparts. Nevertheless, in 2K1C hypertensive rats HRF was found to be lower than normotensive controls (PIP: 64±7 vs. 79±1% and W2: 30±1 vs. 39±1% in 2K1C and normotensive controls, respectively). In conclusion, high blood pressure itself does not affect HRF, although, depending on the model of hypertension used, HRF can be markedly impaired. The interpretation of these findings is challenging, and the high levels of angiotensin in the 2K1C model may affect cardiac pacemaker cells, making their action potentials more stable than unstable. However, the specific mechanisms by which this could happen still need to be studied. Funding Sources: FAPESP, CAPES and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.