Cardiac sympathetic and parasympathetic activity during self-regulation of heart period

Fourteen subjects attempted to increase and 15 attempted to decrease cardiac interbeat interval (IBI) while being provided with biofeedback of IBI, T-wave vector magnitude (TWVM), or respiratory sinus arrhythmia (RSA). Subjects in both groups showed directional change in IBI relative to a tracking control task, but the three types of feedback did not differentially affect performance. Voluntary IBI increases were associated with significant increases in TWVM and RSA, and voluntary IBI decreases were associated with significant reductions in RSA and nonsignificant reductions in TWVM. This pattern of results suggests that alterations in cardiac vagal tone are involved in voluntary IBI increases and decrease tasks. The results also suggest a role for cardiac sympathetic nervous activity in voluntary IBI increase. The role of changing respiration cycle period was also investigated.This research was supported in part by a Department of Psychiatry Medical Student Research Stipend to Courtney German. The design and construction of the biofeedback apparatus used in this research fulfilled in part the requirements for a Master of Science degree in engineering from St. Mary's University by Steve Borcherding.     

Circadian Variation in Cardiac Autonomic Activity: Reactivity Measurements to Different Types of Stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Circadian variation in cardiac autonomic activity: reactivity measurements to different types of stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious humans during spontaneous respiration

Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. However, recent studies showed that, under stress, RSA dissociates from vagal tone, indicating that separate mechanisms might regulate phasic and tonic vagal activity. This dissociation has been linked to the hypothesis that RSA improves pulmonary gas exchange through preferential distribution of heartbeats in inspiration. We examined the effects of hypercapnia and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat distribution throughout the respiratory cycle in 12 volunteers. We found that hypercapnia, but not hypoxemia, was associated with significant increases in heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase remained statistically significant after adjustment for respiratory rate, tidal volume, and HR. Moreover, the RSA amplitude increase was associated with a paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean amplitude ratio derived from spectral analysis, which is consistent with RSA-vagal dissociation. Although hypercapnia was associated with a significant increase in the percentage of heartbeats during inspiration, this association was largely secondary to increases in the inspiratory period-to-respiratory period ratio, rather than RSA amplitude. Additional model analyses of RSA were consistent with the experimental data. Heartbeat distribution did not change during hypoxemia. These results support the concept of RSA-vagal dissociation during hypercapnia; however, the putative role of RSA in optimizing pulmonary perfusion matching requires further experimental validation.     

Effects of auditory stimulus timing in the respiratory cycle on the evoked cardiac response in man at rest

The present experiments were carried out in 21 healthy adults to study the effects of auditory stimulus timing within the respiratory cycle on evoked cardiac response. The stimulus (80 dB white noise) was started by the first and finished by the second R-wave after change in respiratory phase, and presented in different series in either early inspiration or early expiration. The spirogram and eight sequential interbeat intervals (IBI) after respiratory phase change were recorded. The mean of IBI and standard deviation (SD) were calculated separately for each IBI of 20 trials for each subject, during both the prestimulus and poststimulus phases. The stimulus effects were expressed as changes from prestimulus conditions, in terms of delta IBI and delta SD. The mean of each of the eight IBI and its SD were found to vary consistently in the same direction, i.e., SD increased with increasing mean IBI. Stimulation during early inspiration did not produce any effect during this respiratory phase. It was not before the beginning of the following expiration that a significant deceleration was evoked, which was associated with an enhanced delta SD, whereas stimulation during early expiration promptly evoked a biphasic cardiac response of the deceleration - acceleration pattern and an increase and decrease in delta SD, respectively. While SD was found to be a function of age, no such finding was obtained for delta IBI and delta SD. These results are discussed in terms of the "vagal gating" hypothesis.     

The control of pulse transit time independently of interbeat interval by providing feedback from both

Sixteen subjects took part in a two-stage cardiovascular biofeedback experiment. For five sessions all subjects attempted to control their pulse wave transit time(TT), using TT feedback. The eight subjects who achieved control were given a further five sessions, during which they attempted to control their transit time without altering their interbeat interval(IBI) when provided with TT and IBI feedback. No evidence was found for complete dissociation of TT and IBI. When the single TT contingency was in operation, all subjects who had significant control of TT also showed significant changes in IBI in the same direction. When the dual contingency was introduced, subjects either controlled TT but failed to keep IBI stable or kept IBI stable but failed to control TT.     

Self-regulation of respiratory sinus arrhythmia

Respiratory sinus arrhythmia (RSA) — the peak-to-peak variations in heart rate caused by respiration — can be used as a noninvasive measure of parasympathetic cardiac control. In the present study four strategies to increase RSA amplitude are investigated: (1) biofeedback of RSA amplitude, (2) biofeedback of RSA amplitude plus respiratory instructions, (3) respiratory biofeedback, and (4) respiratory instructions only. All four procedures produce a significant increase of RSA amplitude from the first physiological control trial compared to baseline. This increase is faster for the groups that received respiratory biofeedback and respiratory instructions only than for the two groups that received biofeedback of RSA amplitude, the increases being equivalent for the four groups in the third session. All subjects of the group that received biofeedback of RSA amplitude only reported respiratory strategies in order to achieve the increase in RSA. Possible clinical implications of these results for parasympathetic cardiac control and cardiovascular disorders are discussed.This research was supported by a grant to the first author from the University of Granada (Spain).     

Self-regulation of respiratory sinus arrhythmia.

Respiratory sinus arrhythmia (RSA)--the peak-to-peak variations in heart rate caused by respiration--can be used as a noninvasive measure of parasympathetic cardiac control. In the present study four strategies to increase RSA amplitude are investigated: (1) biofeedback of RSA amplitude, (2) biofeedback of RSA amplitude plus respiratory instructions, (3) respiratory biofeedback, and (4) respiratory instructions only. All four procedures produce a significant increase of RSA amplitude from the first physiological control trial compared to baseline. This increase is faster for the groups that received respiratory biofeedback and respiratory instructions only than for the two groups that received biofeedback of RSA amplitude, the increases being equivalent for the four groups in the third session. All subjects of the group that received biofeedback of RSA amplitude only reported respiratory strategies in order to achieve the increase in RSA. Possible clinical implications of these results for parasympathetic cardiac control and cardiovascular disorders are discussed.     

The Effects of Respiratory Sinus Arrhythmia Biofeedback on Heart Rate Variability and Posttraumatic Stress Disorder Symptoms: A Pilot Study

Recent studies have found a significant association between PTSD and low heart rate variability (HRV), a biomarker of autonomic dysregulation. Research indicates that respiratory sinus arrhythmia (RSA) biofeedback increases HRV while reducing related pathological symptoms. This controlled pilot study compared RSA biofeedback to progressive muscle relaxation (PMR) as adjunctive interventions for 38 persons with PTSD symptoms in a residential treatment facility for a substance use disorder. Both groups were assessed at pre-intervention and 4-week post-intervention. Group × time interactions revealed significantly greater reductions in depressive symptoms and increases in HRV indices for the RSA group. Both groups significantly reduced PTSD and insomnia symptoms and a statistical trend was observed for reduced substance craving for the RSA group. Increases in HRV were significantly associated with PTSD symptom reduction. Overall, these results provide preliminary support for the efficacy of RSA biofeedback in improving physiological and psychological health for individuals with PTSD.     

Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus

Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more “rigid”), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves.     

Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse.

In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 6-8 wk; n = 12) [corrected] ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.     

Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control

Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants'' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology.     

The impact of a 6-year comprehensive community trial on the awareness, treatment and control rates of hypertension in Iran: experiences from the Isfahan healthy heart program

Background

Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis.

Methods

Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks.

Results

We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found.

Conclusions

Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect.     

The relationship between respiratory sinus arrhythmia and heart rate during anesthesia in rat.

During inspiration the heart rate (HR) increases and during expiration it decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous heart rate variability (HRV) can be measured as the high frequency (HF) component of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of HR is associated with an increase in HF. The aim of this study was to investigate whether this relationship between HF and HR is preserved during anesthesia in rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to investigate the effect of atropine (N=3), against controls (N=3). Short term HRV was investigated in 30 seconds long epochs. HF was considered the frequency band between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the HF. Respiratory frequency (RF) was quantified as the mean spectral frequency within the HF band. One minute estimates of HR, RSA and HF were calculated by averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3 bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that: (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in HR; (3) the time-dependent increase in RSA is preserved after atropine. We conclude that the correlation between RSA and HR reflects the cardio-pulmonary coupling under parasympathetic control.     

Respiratory Sinus Arrhythmia Versus Neck/Trapezius EMG and Incentive Inspirometry Biofeedback for Asthma: A Pilot Study

This pilot study compared biofeedback to increase respiratory sinus arrhythmia (RSA) with EMG and incentive inspirometry biofeedback in asthmatic adults. A three-group design (Waiting List Control n = 5, RSA biofeedback n = 6, and EMG biofeedback n = 6) was used. Six sessions of training were given in each of the biofeedback groups. In each of three testing sessions, five min. of respiratory resistance and EKG were obtained before and after a 20-min biofeedback session. Additional five-min epochs of data were collected at the beginning and end of the biofeedback period (or, in the control group, self-relaxation). Decreases in respiratory impedance occurred only in the RSA biofeedback group. Traub-Hering-Mayer (THM) waves (.03-.12 Hz) in heart period increased significantly in amplitude during RSA biofeedback. Subjects did not report significantly more relaxation during EMG or RSA biofeedback than during the control condition. However, decreases in pulmonary impedance, across groups, were associated with increases in relaxation. The results are consistent with Vaschillo's theory that RSA biofeedback exercises homeostatic autonomic reflex mechanisms through increasing the amplitude of cardiac oscillations. However, deep breathing during RSA biofeedback is a possible alternate explanation.     

Ventral medullary pH and ventilatory responses to hyperperfusion and hypoxia

The role of a sudden increase in brain perfusion on ventral medullary surface pH (Vm pH) and minute ventilation (VI) was assessed in anesthetized peripherally chemo denervated cats. Acute hypertension (AH), produced by rapid inflation of an aortic balloon, and hypoxemia, produced with either inhalation of 1% CO (COHx) or inhalation of a hypoxic gas (HHx), were used to increase brain blood flow. In the AH group, increasing arterial blood pressure (from 122 +/- 3 to 180 +/- 5 mmHg) caused a rapid (less than 5 s) increase in Vm pH in every trial (n = 18). Associated with the mean peak increases in Vm pH (0.003 +/- 0.0004 pH units) were significant decrease in tidal volume (7-9%). In the COHx group, 17% HbCO caused a significant increase in Vm pH (0.003 +/- 0.0005 pH unit) and diminution of VI (9%). Further increases in HbCO caused a progressive ventral medullary acidosis and greater reductions in VI. The results from the HHX group were qualitatively similar to the COHx group; there was a biphasic response of Vm pH, i.e., an initial increase in Vm pH (0.008 +/- 0.001) followed by a steady decrease in Vm pH, with reductions in VI associated with both phases. We conclude that hyperperfusion, per se, produces an increase in Vm pH and a reduction in VI equivalent in magnitude to that predicted from the CO2 stimulus-response curve; the alkalotic shift in Vm pH and concomitant diminution in VI associated with mild hypoxia is probably related to an increase in ventral medullary perfusion; and the ventilatory depression associated with the medullary acidosis of moderate brain hypoxia must be attributed to another mechanism.     

Incoherent oscillations of respiratory sinus arrhythmia during acute mental stress in humans

Respiratory sinus arrhythmia (RSA) has been widely used as a measure of the cardiac vagal control in response to stress. However, RSA seems not to be a generalized indicator because of its dependency on respiratory parameter and individual variations of RSA amplitude (A(RSA)). We hypothesized that phase-lag variations between RSA and respiration may serve as a normalized index of the degree of mental stress. Twenty healthy volunteers performed mental arithmetic task (ART) after 5 min of resting control followed by 5 min of recovery. Breathing pattern, beat-to-beat R-R intervals, and blood pressure (BP) were determined using inductance plethysmography, electrocardiography, and a Finapres device, respectively. The analytic signals of breathing and RSA were obtained by Hilbert transform and the degree of phase synchronization (λ) was quantified. With the use of spectral analysis, heart rate variability (HRV) was estimated for the low-frequency (LF) and high-frequency (HF) bands. A steady-state 3-min resting period (REST), the first 3 min (ART1), and the last 3 min (ART2) of the ART period (ranged from 6- to 19 min) and the last 3 min of the recovery period (RCV) were analyzed separately. Heart rate, systolic BP, and breathing frequency (f(R)) increased and λ, A(RSA), and HF power decreased from REST to ART (P < 0.01). The λ was correlated with normalized A(RSA) and the HF power. The decrease in λ could not be explained solely by the increase in f(R). We conclude that mental stress exerts an influence on RSA oscillations, inducing incoherent phase lag with respect to breathing, in addition to a decrease in RSA.     

Rac-Induced Left Ventricular Dilation in Thyroxin-Treated ZmRacD Transgenic Mice: Role of Cardiomyocyte Apoptosis and Myocardial Fibrosis

The pathways inducing the critical transition from compensated hypertrophy to cardiac dilation and failure remain poorly understood. The goal of our study is to determine the role of Rac-induced signaling in this transition process. Our previous results showed that Thyroxin (T4) treatment resulted in increased myocardial Rac expression in wild-type mice and a higher level of expression in Zea maize RacD (ZmRacD) transgenic mice. Our current results showed that T4 treatment induced physiologic cardiac hypertrophy in wild-type mice, as demonstrated by echocardiography and histopathology analyses. This was associated with significant increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Conversely, echocardiography and histopathology analyses showed that T4 treatment induced dilated cardiomyopathy along with compensatory cardiac hypertrophy in ZmRacD mice. These were linked with further increases in myocardial Rac-GTP, superoxide and ERK1/2 activities. Additionally, there were significant increases in caspase-8 expression and caspase-3 activity. However, there was a significant decrease in p38-MAPK activity. Interestingly, inhibition of myocardial Rac-GTP activity and superoxide generation with pravastatin and carvedilol, respectively, attenuated all functional, structural, and molecular changes associated with the T4-induced cardiomyopathy in ZmRacD mice except the compensatory cardiac hypertrophy. Taken together, T4-induced ZmRacD is a novel mouse model of dilated cardiomyopathy that shares many characteristics with the human disease phenotype. To our knowledge, this is the first study to show graded Rac-mediated O(2)·(-) results in cardiac phenotype shift in-vivo. Moreover, Rac-mediated O(2)·(-) generation, cardiomyocyte apoptosis, and myocardial fibrosis seem to play a pivotal role in the transition from cardiac hypertrophy to cardiac dilation and failure. Targeting Rac signaling could represent valuable therapeutic strategy not only in saving the failing myocardium but also to prevent this transition process.     

Ventilatory control during exercise in calves with artificial hearts

To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf.     

Voluntary exercise increases IgA concentration and polymeric Ig receptor expression in the rat submandibular gland

Salivary IgA—a primary factor in local immunity of the oral cavity—plays an important role in maintaining local immune function in the oral cavity and prevent upper respiratory tract infections. Oral IgA levels are known to fluctuate in an exercise-dependent manner; thus, we investigated the effects of voluntary exercise on salivary IgA secretion in rats to better understand the mechanism by which this occurs. Six-week-old male Wistar rats were placed in individual cages with or without access to exercise wheels for three weeks. Notably, animals who engaged in voluntary exercise demonstrated significant increases in IgA concentration in saliva and submandibular gland tissue, as well as a markedly higher salivary IgA flow rate. Moreover, active rats also exhibited elevated polymeric Ig receptor (pIgR) mRNA expression in submandibular gland tissue. Collectively, these results suggest that voluntary exercise may increase salivary IgA concentration and boost immune function in the oral cavity.