Increase In Sympathetic Activity Research Articles

The presence of fear: How subjective fear, not physiological changes, shapes the experience of presence.

When we become engrossed in novels, films, games, or even our own wandering thoughts, we can feel present in a reality distinct from the real world. Although this subjective sense of presence is, presumably, a ubiquitous aspect of conscious experience, the mechanisms that produce it are unknown. Correlational studies conducted in virtual reality have shown that we feel more present when we are afraid, motivating claims that physiological changes contribute to presence; however, such causal claims remain to be evaluated. Here, we report two experiments that test the causal role of subjective and physiological components of fear (i.e., activation of the sympathetic nervous system) in generating presence. In Study 1, we validated a virtual reality simulation capable of inducing fear. Participants rated their emotions while they crossed a wooden plank that appeared to be suspended above a city street; at the same time, we recorded heart rate and skin conductance levels. Height exposure increased ratings of fear, presence, and both measures of sympathetic activation. Although presence and fear ratings were correlated during height exposure, presence and sympathetic activation were unrelated. In Study 2, we manipulated whether the plank appeared at height or at ground level. We also captured participants' movements, which revealed that alongside increases in subjective fear, presence, and sympathetic activation, participants also moved more slowly at height relative to controls. Using a mediational approach, we found that the relationship between height exposure and presence on the plank was fully mediated by self-reported fear, and not by sympathetic activation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Correlation of indicators of heart rate autonomic regulation and socio-economic well-being in young people 16–18 years old living in the Arctic zone of the Russian Federation

Background. The impact of natural and climatic factors on human health may change under the influence of other factors related to his socio-economic well-being. The aim of the study. To determine the correlation between indicators of heart rate variability and parameters of socio-economic well-being, quality of life of young people living in the Arctic zone of the Russian Federation (Arkhangelsk).Materials and methods. Parameters of Heart rate variability in 36 young men (16–18 years old) were determined at entry (5 minutes) and at a fixed breath rate (5 minutes). We used the World Health Organization Quality of Life Brief Version of questionnaire, Family Affluence Scale (FAS II) and a questionnaire reflecting the financial situation, composition, and large number of children in the participants’ families.Results. According to correlation analysis, a decrease in the number of family vacations per year and FAS-II scores is accompanied by an increase in sympathetic activity. Indicators of self-perceived health status, number of cars in the family, FAS-II score and family financial status are positively correlated with indicators of vagal activity. Parameters of the psychological sphere of life quality and family composition were negatively correlated with sympathetic activity; parameters of the physical sphere of life quality and the number of family vacations per year were negatively correlated with vagal activity (fixed breath rate).Conclusion. We identified specific indicators of socio-economic well-being that are most closely related to both the tension of the cardiac activity mechanisms and the decrease in vagal reserves of autonomic regulation in young men living in the Russian Arctic.

Carotid body-mediated peripheral chemoreflex drive sets exercise tolerance in adult mice

Exercise tolerance (EXT) has been primarily explained by individual body/physical features, partly neglecting the complex cardiorespiratory response needed to cope with exercise. While in healthy conditions most people display good EXT, the presence of exercise intolerance (EXINT) has also been documented. More importantly, EXINT increases in several pathological conditions. Despite the precise mechanism underpinning EXINT is not fully understood. It is well known that exaggerated sympathetic outflow to skeletal muscle impairs proper muscle function and that activation of the carotid body (CB) chemoreceptors elicits a robust increase in sympathetic activity. Therefore, it is plausible to hypothesize that an exaggerated CB-chemoreflex drive may impair EXT. Accordingly, we aimed to determine: i) differences in CB-chemoreflex drive between EXT and EXINT mice, and ii) the role played by the CB-chemoreflex on setting EXINT. Male C57/BL6 mice (n=24) were used to study chemoreflex function using whole-body plethysmography. Exercise tolerance/intolerance was determined by a three-day maximal performance exercise test. CB-chemoreflex drive was assessed by allowing the mice to breathe hypoxic gas (FiO2~5%). We found that the incidence of EXINT among healthy mice was ~30%. Notably, compared to EXT mice, animals with EXINT exhibited a heightened CB-mediated chemoreflex drive as evidenced by larger increases in the hypoxic ventilatory responses (HVR). Indeed, HVR was ~1.4-fold larger in EXINT compared to the values obtained in EXT mice (VE: 17 ± 1.6 vs. 12 ± 3.2, mL/min, EXINT vs. EXT, respectively). Then, we tested whether high chemoreflex drive was associated with EXINT. For this, we reduced the chemosensory drive by using the Dejour´s maneuver (FiO2~35%) while EXINT mice continues to exercise. We found that chemoreflex unloading in EXINT markedly improves exercise tolerance. Indeed, exercise tolerance was almost fully restored by reducing chemoreflex drive in EXINT. Our findings underscore the potential role of heightened CB-chemoreflex on setting exercise tolerance. Supported by Fondecyt 1220950. 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.

IN ARTERIAL HYPERTENSION THE RIGHT VENTRICLE IS NO LONGER THE “FORGOTTEN CAVITY”

Objective: The right ventricle showed late interest in the assessment and stratification of the severity of arterial hypertension. The complex systemic reaction in the context of arterial hypertension, represented in particular by the activation of the renin angiotensin aldosterone system and the increase in sympathetic activity would suggest an early impairment of diastolic and later systolic function also of the right ventricle. Echocardiography is the most accessible way to evaluate the right ventricle in medical practice. Purpose of the study: to evaluate the precocity and the type of right ventricular function impairment in recently diagnosed hypertensive patients. Design and method: The patients were included after following the recommendations for the diagnosis of arterial hypertension according to the guide published by ESH in 2023. Personal biological data and parameters, cardiovascular risk factors, blood pressure values were recorded. Patients with other comorbidities, with secondary hypertension were excluded.Patients on antihypertensive treatment were also excluded. We investigated echocardiographically by analyzing 2D diastolic parameters, Doppler spectral and mitral and tricuspid tissue parameters as well as the global longitudinal strain of both ventricles. We studied right ventricle global longitudinal strain (RVGLS), septal wall longitudinal strain (RVSWLS), right ventricle lateral wall longitudinal strain (RVLWLS). Results: we studied a group of 61 patients who presented with essential hypertension, recently diagnosed, with an average age of 68.1 +- 6.3 years and who were analyzed according to grade, gender, risk factors. The (RVGLS) was analyzed separately and comparatively for the lateral and septal wall and the values were RVGLS =19%+- 3.2%. RVSWLS=-13.1% +-2.9% and RVFWLS=-22.6%+- 3.4%. The filling ratio of the right ventricle E/e’ was 14. Conclusions: the diastolic function of the right ventricle is affected in recently diagnosed hypertensive patients in relation to the degree of hypertension, myocardial mass and the filling ratio of the left ventricle. Slightly increased values of RVLWGLS could be interpreted as a consequence of sympathetic activation

High altitude sojourn elicits divergent effects in aortic and carotid stiffness in healthy-young adults

High altitude exposure challenges the cardiovascular system to compensate for barometric pressure-mediated reductions in arterial oxygen content. Reductions in oxygen content elicit simultaneous increases in sympathetic nervous system activity and vasodilation that may have competing effects on changes in large artery stiffness. The objective of this study was to examine changes in aortic and carotid stiffness during high altitude sojourn in healthy, young adults. We hypothesized that short-term high-altitude sojourn would increase both aortic and carotid stiffness. 17 Generally healthy adults (23±4 yrs, 25.0±3.0 BMI, n=9 females) underwent vascular assessments in the supine position at 1400 m and after an 8-day incremental ascent to 4300 m. Aortic stiffness and carotid β-stiffness were derived from carotid-femoral pulse wave velocity (cfPWV) via applanation tonometry and right common carotid artery ultrasonography, with blood pressure assessed via oscillometry. Ascent from 1400 m to 4300 m resulted in decreased arterial oxygen saturation (-11±4 %, p<0.001) and carotid β-stiffness (-4.48±2.73 au, p<0.001), and increased cfPWV, (+54.98±78.10 cm/s, p=0.01) and mean arterial pressure (+4±7 mmHg, p=0.02). Changes in cfPWV, arterial oxygen saturation, and blood pressure were moderately to strongly correlated (r=-0.425-0.503, p=0.09-0.04). Our data suggest that short term exposure to high altitude has differential effects on carotid versus aortic stiffness despite increases in mean blood pressure. Increases in aortic stiffness appear related to hypoxia-induced reductions in arterial oxygen saturation and concomitant increases in blood pressure, while reductions in carotid stiffness may stem, in-part, from compensatory carotid artery dilation necessary to increase cerebral blood flow at high altitude. Additional research is necessary to further understand mechanisms underlying differential changes in large artery stiffness during high altitude sojourn. 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.

EGCG’s effects on Mean Arterial Pressure and Heart Rate Variability and Their Correlations with Metabolic and Hormonal Profiles in Obese Subjects

This study aimed to investigate the effects of epigallocatechin gallate (EGCG), a potent polyphenol found in green tea, on mean arterial pressure (MAP) and heart rate variability (HRV) in obese subjects along with their associations with metabolic factors. We hypothesized that EGCG treatment could significantly reduce MAP and sympathetic tone, represented by decreased low-frequency power (LF) and LF-to-high frequency power (HF) ratio. Furthermore, we expected that systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP would be positively correlated with obesity parameters, LF, and LF-to-HF ratio. This study is a double-blind, randomized controlled trial. Thai obese subjects with a body mass index (BMI) ≥ 25 kg/m2 (criteria for an Asian population) were randomly allocated into EGCG and placebo groups and received a capsule of 150 mg of EGCG or starch, respectively, twice a day without any dietary restrictions. Clinical and anthropometric data, as well as spontaneous 5-minute HRV measurements in both time and frequency domains, were assessed at baseline (week 0), week 4, and week 8. Additionally, 8-hour fasting blood samples were collected at weeks 0 and 8 to measure metabolic and hormonal levels. EGCG treatment for 8 weeks significantly reduced MAP compared to week 0 and week 4 (P < 0.05 for all). In the EGCG treatment group, there was a significant increase in the LF-to-HF ratio and a nonsignificant decrease in HF at week 8 compared to week 0. LF showed a trend toward increasing in week 8 of EGCG treatment compared to week 4. For correlation analysis at week 0, SBP had significant positive correlations with BMI, percent fat, fat mass, serum leptin and insulin levels, and the homeostatic model assessment for insulin resistance (HOMA-IR) (R = 0.468-0.593, p<0.05 for all) but had negative correlations with the quantitative insulin sensitivity check index (QUICKI) and HDL-cholesterol (R = (-0.437)-(-0.468), P <0.05 for all). DBP was positively correlated with age and HF in normal units (nu) (R = 0.412-0.568, p<0.05 for all), but was negatively correlated with height, HDL-cholesterol, LF in ms (R = (-0.379)-(-0.509), P <0.05 for all). MAP showed significant positive correlations with age, BMI, percent fat, fat mass, serum leptin levels, and HOMA-IR (R = 0.370-0.459, P < 0.05 for all), but had a negative correlation with HDL-cholesterol (R = -0.522, P = 0.004). EGCG treatment over an 8-week duration reduced MAP, a pivotal component of overall blood pressure in obese individuals, and exhibited a significant increase in the LF/HF ratio, tending toward an increase in LF and a non-significant decrease in HF. We postulate that the decrease in MAP may be attributed to EGCG's direct or indirect vasodilatory effects, potentially through the stimulation of nitric oxide production, reduced oxidative stress, and/or decreased levels of kisspeptin, a vasoconstrictive substance, as reported by previous studies. An increase in the LF/HF ratio could reflect a shift toward sympathetic nervous system dominance (LF) and/or a decrease in parasympathetic nervous system activity (HF) indicating a compensatory response to the reduced blood pressure post-vasodilation. HDL cholesterol showed negative correlations with SBP, DBP, and MAP, reflecting its protective benefit against high blood pressure. In summary, 8 weeks of EGCG treatment resulted in a significant decrease in MAP and an increase in the LF/HF ratio, reflecting EGCG’s primary vasodilatory effects and a compensatory increase in sympathetic nervous system activity. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012). 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.

Pharmacological Modulation of Leg Shear Rate Profile in Young and Older Adults

Aging alters the shear rate profile in the arm, characterized by increased oscillatory (bidirectional) shear, potentially from progressive increases in sympathetic nervous system activity. However, the extent to which the shear profile in the atheroprone vasculature of the leg is mediated by sympathetic overactivity via α-adrenergic receptor activation is unknown. We sought to determine how pharmacological modulation of α-adrenergic receptor activity alters shear in the femoral artery with aging. We hypothesized, within the leg, that increased α-adrenergic vasoconstriction would lead to a pro-atherosclerotic shear profile in young adults while α-adrenergic blockade would improve the shear rate profile in older adults, as previously reported in the arm. Resting femoral artery shear rate profiles were assessed in five young (4M/1F, 26±5 yr) and seven older (4M/3F, 65±7 yr) adults during saline (control), phentolamine (PHEN, nonselective α -adrenergic antagonist), and phenylephrine (PE, a selective α-adrenergic agonist) intra-arterial infusions using Doppler ultrasound. Under control conditions, there were no age-related differences in antegrade, retrograde, or total (antegrade + retrograde) shear rates. During PHEN infusion, antegrade shear increased in both young and older adults (Y: 597±214 v. 1011±313 s−1; O: 412±168 v. 648±334 s−1, p<0.05 for both), while retrograde (Y: 122±49 v. 62±21 s−1; O: 109±59 v. 54±43 s−1, p<0.05 for both), and oscillatory shear decreased (Y: 0.17±0.01 v. 0.06±0.01; O: 0.20±0.02 v. 0.09±0.02, p<0.05 for both) compared to control. Although the magnitude of change was similar between age groups, antegrade and total shear were greater in young following PHEN. Infusion of PE had no effect on antegrade (Y: p=0.16; Op=0.78,), retrograde (Y: p=0.83; O: p=0.17), and oscillatory shear (Y: p=0.25; O: p=0.09) but did cause an age-related separation in antegrade and total shear such that the young were greater following PE. Collectively, these preliminary data suggest withdrawal of α-adrenergic vasoconstriction with PHEN leads to a more favorable shear pattern (i.e., increased antegrade shear, and decreased retrograde and oscillatory) within the femoral artery, independent of age. Overall, these findings indicate that femoral shear rate may be influenced by the α-adrenergic system in a manner that is uniquely different from what has been previously reported in the arm. R01HL142603, I01CX001999, IK2RX001215. 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.

Effect of series of periodic limb movements in sleep on blood pressure, heart rate and high frequency heart rate variability.

The phenomenon known as periodic limb movements in sleep (PLMS) has been linked to a change in autonomic nervous system (ANS) activity and its effect on circulatory regulation. Autonomic dysfunction or dysregulation in patients with PLMS has been described in some domains; however, any relationship between heart rate variability (HRV) and PLMS has not been clearly established. HRV analysis is a recognised, non-invasive research method that describes the influence of the ANS on heart rate (HR). The aim of our study was to further investigate the dysregulation of autonomic HR control in patients with PLMS. We undertook a retrospective analysis of the polysomnographic (PSG), demographic and medical data of five patients with a total number of 1,348 PLMS. We analysed HR, HRV HF, systolic blood pressure (SBP), and diastolic blood pressure (DBP) for 10 heartbeats before the series of PLMS and 10 consecutive heartbeats as beat-to-beat measurements. The presented method of using successive, short, 10 RR interval segments refers to the time-frequency measurement, which is very clear and useful for presenting changes in the calculated parameters over time and thereby illustrating their dynamics. This method allowed us to assess dynamic changes in HRV HF during successive PLMS series. Statistical analysis was performed using IBM SPSS Statistics (v. 28.0.0.0). The Kruskal-Wallis test was performed to find statistically significant changes from baseline. No statistically significant changes in HR, SBP, or DBP were found in our group, although an increase in the value of the HRV HF was noted, suggesting an increase in intracardiac parasympathetic activity during the subsequent series of PLMS. Our study indicates an increase in parasympathetic activity during the appearance of successive PLMS, which, with the simultaneous lack of changes in HR, may suggest an increase in sympathetic activity, and therefore the appearance of so-called 'autonomic co-activation' resulting in the possibility of life-threatening cardiac events. Our findings add to the literature information regarding HRV in PLMS, and highlight the need for further studies to elucidate the effects of these conditions on the ANS, and on cardiovascular health.

The emotion paradox in the aging body and brain.

With age, parasympathetic activity decreases, while sympathetic activity increases. Thus, the typical older adult has low heart rate variability (HRV) and high noradrenaline levels. Younger adults with this physiological profile tend to be unhappy and stressed. Yet, with age, emotional experience tends to improve. Why does older adults' emotional well-being not suffer as their HRV decreases? To address this apparent paradox, I present the autonomic compensation model. In this model, failing organs, the initial phases of Alzheimer's pathology, and other age-related diseases trigger noradrenergic hyperactivity. To compensate, older brains increase autonomic regulatory activity in the pregenual prefrontal cortex (PFC). Age-related declines in nerve conduction reduce the ability of the pregenual PFC to reduce hyperactive noradrenergic activity and increase peripheral HRV. But these pregenual PFC autonomic compensation efforts have a significant impact in the brain, where they bias processing in favor of stimuli that tend to increase parasympathetic activity (e.g., stimuli that increase feelings of safety) and against stimuli that tend to increase sympathetic activity (e.g., threatening stimuli). In summary, the autonomic compensation model posits that age-related chronic sympathetic/noradrenergic hyperactivity stimulates regulatory attempts that have the side effect of enhancing emotional well-being.

Resistance Training to Muscle Failure with Variable Load Intensities: Implications for Post-Exercise Blood Pressure and Heart Rate Variability in Trained Men.

Background: The modulation of cardiac sympathovagal balance alters following acute resistance training (RT) sessions. Nevertheless, the precise influence of RT at varying load intensities on this physiological response remains to be fully elucidated. Therefore, the aim of this study was to compare the time course of recovery following low- (40%), moderate- (60%), and high- (80%) load-intensity RT protocols performed up to muscle repetition failure in resistance-trained men. Method: Sixteen young, resistance-trained men (mean age: 21.6 ± 2.5 years, mean height: 175.7 ± 8.9 cm, mean weight: 77.1 ± 11.3 kg) participated in a randomized crossover experimental design involving three sessions, each taken to the point of muscle failure. These sessions were characterized by different load intensities: low (40% of 1-repetition maximum, 1RM), moderate (60% of 1RM), and high (80% of 1RM). The exercise regimen comprised four exercises-back squat (BS), bench press (BnP), barbell row (BR), and shoulder press (SP)-with each exercise consisting of three sets. Throughout each session, heart rate variability (HRV) and blood pressure (BP) parameters were assessed both pre-exercise and during a 40 min post-exercise period, segmented into 10 min intervals for stabilization. Statistical analysis involved the use of a repeated measures ANOVA. Results: It was observed that the 40% and 60% RT sessions resulted in a significantly higher root mean square of successive R-R intervals (RMSSD) value compared to the 80% RT session in the post-exercise recovery process in 30 min (respectively, p = 0.025; p = 0.028) and 40 min (respectively, p = 0.031; p = 0.046), while the 40% and 60% RT sessions produced similar responses. The 40% RT session was significantly higher in the high frequency (HF) value post-exercise in 40 min compared to the 80% RT session (p = 0.045). Conclusions: Our findings suggest that engaging in resistance training (RT) sessions to muscle failure at an intensity of 80% induces acute increases in sympathetic activity, potentially leading to elevated cardiovascular stress. For individuals with normal blood pressure, it is advisable to opt for lighter loads and higher repetition volumes when prescribing RT, as heavier-load RT may carry an increased risk of cardiac-related factors.

Results of surgical treatment of hernias of the anterior abdominal wall in patients with connective tissue dysplasia syndrome

Relevance. The problem of surgical treatment of hernias of the anterior abdominal wall remains relevant. Despite the introduction of new technologies, the results of surgical interventions cannot be considered satisfactory. The development of hernias and their relapses is facilitated by connective tissue dysplasia syndrome, which manifests as phenotypic signs, disorders of the autonomic nervous system, and morphological changes in the structure of the connective tissue.Objective. To improve the results of surgical treatment of hernias of the anterior abdominal wall in patients with connective tissue dysplasia syndrome.Materials and methods. The study was based on clinical observations and studies of 497 patients with hernias of the anterior abdominal wall. Inguinal (29 %) and postoperative hernias (21 %) predominated. In the structure of recurrent hernias, postoperative (47 %) and inguinal (42 %) hernias were more often observed. Hernioautoplasty was performed in 31 %, plastic surgery using a mesh endoprosthesis — in 54 %, endoscopic hernioplasty — in 15 % of patients. The severity of the clinical, morphological, and metabolic signs of connective tissue dysplasia syndrome was assessed. The concentration of free hydroxyproline in the blood was determined as a marker of connective tissue metabolism. The state of the autonomic nervous system was assessed using variational pulsometry. To assess the state of collagen in connective tissue, a morphological study of the aponeuroses of the muscles of the anterior abdominal wall was performed in the clinic and experiment.Results. The overall incidence of dysplasia in hernias of the anterior abdominal wall was 48 %. The highest incidence of connective tissue dysplasia was detected in recurrent hernias (70 %). Studies of the level of free hydroxyproline in abdominal hernias have shown the dependence of this marker on the degree of connective tissue dysplasia. In cases of recurrent hernias, the highest intensity of collagen biodegradation was observed. A study of the functional state of the autonomic nervous system revealed a predominance of sympathetic activity in abdominal wall hernias with an increase in the tension index by more than 4 times. An increase in the severity of dysplasia is accompanied by an increase in sympathetic activity. Histological studies in patients with abdominal hernias revealed characteristic changes in the morphological structure of the connective tissue. The average thickness, specific area, brightness of staining, and orientation of collagen fibers in postoperative and recurrent hernias were significantly different compared to the group with primary hernias (p˂0.05). Additionally, an experiment was performed on 30 laboratory animals (white rats) to determine the optimal conditions for healing of the aponeurosis of the anterior abdominal wall. The activating effect of prozerin on the process of histogenesis in the wound was revealed. Based on the results of the study, the surgical treatment of hernias was assessed depending on the type of hernioplasty and the severity of connective tissue dysplasia. It has been established that with increasing severity of dysplasia, the frequency of relapses increases by 2.2–3.4 times. With the progression of dysplasia, the frequency of relapses increased by more than twice. The use of the endoscopic hernioplasty method reduced the risk of recurrent hernias by 9 times.Conclusion. In externally localized hernias, the incidence of connective tissue dysplasia ranges from 34 % to 70 %. In patients with connective tissue dysplasia syndrome after hernia autoplasty, the frequency of hernia recurrence is 3.4 times higher. Drug correction of sympathetic activity along with alloplasty increased collagen synthesis intensity by 36 %. The choice of hernia repair method should be determined by the type of hernia, the age of the patient, and the severity of connective tissue dysplasia.

Sympathetic innervation induces exosomal miR-125 transfer from osteoarthritic chondrocytes, disrupting subchondral bone homeostasis and aggravating cartilage damage in aging mice

IntroductionOsteoarthritis (OA) is a progressive disease that poses a significant threat to human health, particularly in aging individuals: Although sympathetic activation has been implicated in bone metabolism, its role in the development of OA related to aging remains poorly understood. Therefore, this study aimed to investigate how sympathetic regulation impacts aging-related OA through experiments conducted both in vivo and in vitro. MethodsTo analyze the effect of sympathetic regulation on aging-related OA, we conducted experiments using various mouse models. These models included a natural aging model, a medial meniscus instability model, and a load-induced model, which were used to examine the involvement of sympathetic nerves. In order to evaluate the expression levels of β1-adrenergic receptor (Adrβ1) and sirtuin-6 (Sirt6) in chondrocytes of naturally aging OA mouse models, we performed assessments. Additionally, we investigated the influence of β1-adrenergic receptor knockout or treatment with a β1-adrenergic receptor blocker on the progression of OA in aging mice and detected exosome release and detected downstream signaling expression by inhibiting exosome release. Furthermore, we explored the impact of sympathetic depletion through tyrosine hydroxylase (TH) on OA progression in aging mice. Moreover, we studied the effects of norepinephrine(NE)-induced activation of the β1-adrenergic receptor signaling pathway on the release of exosomes and miR-125 from chondrocytes, subsequently affecting osteoblast differentiation in subchondral bone. ResultsOur findings demonstrated a significant increase in sympathetic activity, such as NE levels, in various mouse models of OA including natural aging, medial meniscus instability, and load-induced models. Notably, we observed alterations in the expression levels of β1-adrenergic receptor and Sirt6 in chondrocytes in OA mouse models associated with natural aging, leading to an improvement in the progression of OA. Critically, we found that the knockout of β1-adrenergic receptor or treatment with a β1-adrenergic receptor blocker attenuated OA progression in aging mice and the degraded cartilage explants produced more exosome than the nondegraded ones, Moreover, sympathetic depletion through TH was shown to ameliorate OA progression in aging mice. Additionally, we discovered that NE-induced activation of the β1-adrenergic receptor signaling pathway facilitated the release of exosomes and miR-125 from chondrocytes, promoting osteoblast differentiation in subchondral bone. ConclusionIn conclusion, our study highlights the role of sympathetic innervation in facilitating the transfer of exosomal miR-125 from osteoarthritic chondrocytes, ultimately disrupting subchondral bone homeostasis and exacerbating cartilage damage in aging mice. These findings provide valuable insights into the potential contribution of sympathetic regulation to the pathogenesis of aging-related OA.

Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

A Comprehensive Insight on Pharmacological Properties of Cilnidipine: A Fourth-generation Calcium Channel Blocker

Abstract: Preventing the development of cardiovascular problems is a key objective of antihypertensive drugs. Many of the non-pressure related coronary risk factors for hypertension are thought to be connected to an increase in sympathetic activity. The sympathetic systems have N-type calcium channels at the nerve terminals that control neurotransmitter release. Cilnidipine is a unique fourth-generation calcium channel blocker with blocking action on both L-/N- type calcium channels. Several L-type calcium channel blockers (Nilvadipine, amlodipine, azelnidipine, nifedipine, etc.) have been used to treat hypertensive patients. Cilnidipine is a novel drug that exerts a hypotensive effect through vasodilation action via blocking L-type calcium channels and potent antisympathetic activity via blocking N-type calcium channels. Inhibiting N-type calcium channels might be a new approach to treating cardiovascular disorders. Therefore, it is expected that cilnidipine may respond well to complicated hypertension. The present review aims to describe the management mechanism of hypertension, and other pharmacological and physicochemical properties of cilnidipine. Cilnidipine has various other beneficial effects such as lipid-lowering effect, reduced white coat effect, improves insulin sensitivity in essential hypertensive patients, ameliorates osteoporosis in ovariectomized hypertensive rats, reduced arterial stiffness, reduced the risk of pedal edema, antinociceptive effects, neuroprotective and renal protective effect, probably through inhibition of N-type calcium channels. Cilnidipine distinguishes itself from other calcium channel blockers due to its wide range of beneficial pharmacological effects. In conclusion, cilnidipine may be more advantageous than other dihydropyridines, such as nisoldipine, amlodipine, azelnidipine, and other antihypertensive drugs.

Heart Rate Variability-Based Prediction of Autonomic Dysreflexia After Spinal Cord Injury.

Autonomic dysreflexia (AD) is a common autonomic complication of spinal cord injury (SCI) characterized by a sudden increase is blood pressure triggered by peripheral stimulation, such as bladder distention. Iatrogenic AD events often occur during various medical procedures including urodynamic assessments (UDSs) used to evaluate lower urinary tract (LUT) function in individuals with SCI. To date, there are no established clinical practices that would allow early detection of the development of episodes of AD. Heart rate variability (HRV) is a reliable and non-invasive metric for evaluating autonomic regulation of the cardiovascular system, with demonstrated utility in people with SCI during UDSs. We aim to provide a comprehensive evaluation of cardiovascular function during UDS-induced AD using ultra-short-term HRV analysis and identify changes in cardiovascular dynamics to predict the onset of AD. We assessed cardiovascular data in a total of 24 participants with sensorimotor complete SCI above T6 (17 males, 7 females, median age = 43 [36-50] years) who experienced AD during UDS. We used continuous electrocardiographic recordings to evaluate HRV in 60 sec overlapping windows during filling cystometry. The mean of "normal-to-normal" heartbeats (meanNN), its standard deviation (SDNN), and the root mean square of successive differences (RMSSD) were calculated and used in all subsequent analyses. We found that SDNN and RMSSD diminished during the early phase of bladder filling and sharply increased during AD. Using the lowest point of statistical variability in heart rate (i.e., SDNN), we were able to predict AD events within 240 sec (percentile 25-percentile 75: 172-339 sec) before the first systolic blood pressure peak after AD onset (sensitivity = 0.667; specificity = 0.875). Our results indicated a temporary increase in sympathetic activity during the early phase of bladder filling, which is followed by an increase in parasympathetic outflow to the heart when AD occurs. These findings have significant clinical implications that extend beyond the context of UDS and demonstrate the importance of identifying early changes in HRV in order to accurately predict AD episodes in people living with SCI.

The effects of anesthetic drug choice on heart rate variability and echocardiography parameters in cats

Heart rate variability (HRV) is one of the assessments of cardiovascular risk during general anesthesia. This study aimed to assess the effects of an anesthetic drug on HRV in cats and to provide information for clinical applications. Twenty-four healthy client-owned cats of various breeds, 12 females and 12 males scheduled for elective surgery, were enrolled in this study. The cats were premedicated and induced with 4 protocols: protocol 1, diazepam (0.3 mg/kg) and propofol (2–4 mg/kg) IV; protocol 2, diazepam (0.3 mg/kg) and alfaxalone (1–3 mg/kg) IV; protocol 3, diazepam (0.3 mg/kg) and ketamine (3–5 mg/kg) IV; and protocol 4, xylazine (1 mg/kg) and tiletamine/zolazepam (Zoletil) (5 mg/kg) IM. The heart rate and HRV of the 24 cats were collected before and at least 1 h after administering the anesthetic drugs. Echocardiography was performed to evaluate heart function. Oscillometric blood pressure monitoring was used to obtain the mean blood pressure. After anesthetic drug administration, higher heart rates were found in cats premedicated and induced with alfaxalone (p = 0.045) than in the other protocols. The lowest heart rate (HR) values were found in cats in protocol 4 using xylazine and Zoletil. The HRV low frequency (LF) and high frequency (HF) power ratios increased in all protocols except for cats premedicated and intubated with propofol. The standard deviation of the regular sinus beats (SDNN) was higher in cats premedicated and induced with ketamine than in other anesthetic protocols (p = 0.015). An increase in sympathetic activity and reduced HRV is associated with high blood pressure and left atrial dimension. The percentage of fractional shortening (FS) decreased in cats premedicated with ketamine. The results showed that the anesthesia method using diazepam and propofol caused the least disturbance of HRV compared with other anesthesia methods that were used in this study.

THE EMOTION PARADOX IN THE AGING BODY AND BRAIN

Abstract With age, parasympathetic activity decreases while sympathetic activity increases. Thus, the typical older adult has low heart rate variability (HRV) and high noradrenergic activity. Younger adults with this physiological profile tend to be chronically unhappy and stressed. Yet, with age, emotional experience tends to improve. Why doesn’t older adults’ emotional well-being suffer as their HRV decreases? To address this apparent paradox, I present the autonomic compensation model. In this model, failing organs and initial phases of Alzheimer’s pathology trigger noradrenergic hyperactivity in older adults. Older brains attempt to compensate by increasing autonomic regulatory processes in ventromedial prefrontal (vmPFC) cortex. Age-related declines in nerve conduction reduce the ability of these compensatory attempts to reduce hyperactive noradrenergic activity and increase peripheral HRV. However, despite their muted effects on peripheral autonomic activity, these autonomic compensation attempts bias brain processing in favor of stimuli that tend to increase parasympathetic activity and against stimuli that tend to increase sympathetic activity. The autonomic compensation model can account for the “age-related positivity effect” in which, compared with younger adults, older adults show attentional and memory biases favoring positive over negative stimuli. Consistent with the autonomic compensation model, the age-related positivity effect is associated with vmPFC activity and functional connectivity and is evident even in early attention processes resistant to goal-directed processing. The autonomic compensation model posits that the aging brain responds to sympathetic hyperactivity in ways that amplify on-going automatic emotion regulation processes and so help maintain emotional well-being.

Hypertension in periand postmenopausal women: mechanisms, management, observation

An important role in the development and evolution of hypertension in females is applied to sex hormones. Estrogen deficiency and hyperandrogenism, characteristic of periand postmenopause, are links in the pathogenesis of hypertension in this period of a woman's life and are accompanied by an increase in sympathetic nervous system activity, renin-angiotensin-aldosterone system activation, salt sensitivity, abdominal obesity and metabolic syndrome, left ventricle hypertrophy, left atrial dilatation with a high risk of atrial fibrillation, stroke and heart failure development. The paper discusses antihypertensive therapy during periand postmenopause, effectiveness and tolerability of different drug classes. Special attention is paid to the mechanism of action of selective I1-imidazoline receptor agonist moxonidine, which in women during this period both effectively reduces high blood pressure and has a beneficial metabolic effect, what is documents in studies of monotherapy, combined antihypertensive therapy with major classes and in combination with menopausal hormone therapy. The paper presents the joint expert opinion concerning above mentioned issues.

The effect of mindfulness meditation on dental anxiety during implant surgery: a randomized controlled clinical trial

Dental implant surgery is almost always associated with patient anxiety. Anxiety during dental surgical procedures triggers an increase in sympathetic activity. Mindfulness meditation (MM) is often associated with high levels of relaxation in the form of increased parasympathetic tone and decreased sympathetic activity. However, the effect of MM on dental anxiety is not clear. The current study aimed to show the effects of a MM as a sedative technique during dental implant surgery by examining the State-Trait Anxiety Inventory (STAI-S), bispectral index (BIS), cortisol levels (CL), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and saturation (SpO2) parameters. HR, SBP, DBP, SpO2, BIS score and CLs were compared at the baseline, immediately before-, during-, and immediately after surgery between the test and control groups. We found that the MM resulted in significant decrease in BIS together with positive effects on hemodynamic parameters (decrease of HR, SBP, DBP and increase of SpO2), psychological findings (improvement on STAI-S scores) and biochemical outcomes (decreased CL). In conclusion, the results demonstrate that MM appeared to be a reliable strategy for managing stress during dental implant operation with benefits in psychological, physiological and biochemical outcomes.

Autonomic nervous system activity in response to stress and cardiac coherence breathing exercise depending on body composition differences

ABSTRACT This study investigated the effects of stress and cardiac coherence breathing exercises on psychological and psychophysiological responses, and also determined whether these effects differed depending on body composition. The study participants included 33 individuals with a favourable body composition in the fit group and 25 individuals with a less favourable body composition in the unfit group. Before the experiment, the participants completed psychological questionnaires to determine psychological differences at baseline. We recorded an electrocardiogram to analyze heart rate variability (HRV) for five minutes under three conditions: rest, an arithmetic task to induce stress, and a breathing exercise. This was followed by measurements of stress, anxiety, relaxation, and confidence using the visual analogue scale. Baseline analyses revealed that the fit group had lower depression, state and trait anxiety, and stress levels than the unfit group. The HRV indices of the standard deviation of the N-N interval (SDNN) and the root mean square of successive difference (RMSSD) decreased during the arithmetic task with increased stress and heart rate. In contrast, the breathing exercise increased SDNN, RMSSD, total power, and low-frequency power, reduced anxiety and stress, and increased relaxation and confidence. The stress condition and breathing exercise affected the groups differently. The fit group demonstrated a more significant increase in sympathetic activity during stress situations, followed by a greater increase in parasympathetic activity and recovery from stress during the breathing exercise. These findings illustrate that individuals with a more favourable body composition may have greater autonomic nervous system adaptability.