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2.
Am J Physiol Regul Integr Comp Physiol ; 327(1): R1-R13, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38738293

ABSTRACT

Hypoxia is a pivotal factor in the pathophysiology of various clinical conditions, including obstructive sleep apnea, which has a strong association with cardiovascular diseases like hypertension, posing significant health risks. Although the precise mechanisms linking hypoxemia-associated clinical conditions with hypertension remains incompletely understood, compelling evidence suggests that hypoxia induces plasticity of the neurocirculatory control system. Despite variations in experimental designs and the severity, frequency, and duration of hypoxia exposure, evidence from animal and human models consistently demonstrates the robust effects of hypoxemia in triggering reflex-mediated sympathetic activation. Both acute and chronic hypoxia alters neurocirculatory regulation and, in some circumstances, leads to sympathetic outflow and elevated blood pressures that persist beyond the hypoxic stimulus. Dysregulation of autonomic control could lead to adverse cardiovascular outcomes and increase the risk of developing hypertension.


Subject(s)
Hypoxia , Reflex , Humans , Hypoxia/physiopathology , Animals , Reflex/physiology , Sympathetic Nervous System/physiopathology , Blood Pressure/physiology , Hypertension/physiopathology , Autonomic Nervous System/physiopathology , Cardiovascular System/physiopathology , Cardiovascular System/innervation
3.
J Neuroeng Rehabil ; 21(1): 83, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38802939

ABSTRACT

BACKGROUND: Gait deficits are very common after stroke and therefore an important aspect in poststroke rehabilitation. A currently little used method in gait rehabilitation after stroke is the activation of the flexor reflex (FR) by electrical stimulation of the sole of foot while walking. The aim of this study was to investigate the effect of FR stimulation on gait performance and gait parameters in participants with stroke within a single session of flexor reflex stimulation using Incedo™. METHODS: Twenty-five participants with subacute (n = 14) and chronic (n = 11) stroke were enrolled in the study. Motor functions were tested with a 10-m walk test (10mWT), a 2-min walk test (2minWT), and a gait analysis. These tests were performed with and without Incedo™ within a single session in randomized order. RESULTS: In the 10mWT, a significant difference was found between walking with Incedo™ (15.0 ± 8.5 s) versus without Incedo™ (17.0 ± 11.4 s, p = 0.01). Similarly, the 2minWT showed a significant improvement with Incedo™ use (90.0 ± 36.4 m) compared to without Incedo™ (86.3 ± 36.8 m, p = 0.03). These results indicate that while the improvements are statistically significant, they are modest and should be considered in the context of their clinical relevance. The gait parameters remained unchanged except for the step length. A subgroup analysis indicated that participants with subacute and chronic stroke responded similarly to the stimulation. There was a correlation between the degree of response to electrostimulation while walking and degree of improvement in 2minWT (r = 0.50, p = 0.01). CONCLUSIONS: This study is the first to examine FR activation effects in chronic stroke patients and suggests that stimulation effects are independent of the time since stroke. A larger controlled clinical trial is warranted that addresses issues as the necessary number of therapeutical sessions and for how long stimulation-induced improvements outlast the treatment period. TRIAL REGISTRATION: The trial was retrospectively registered in German Clinical Trials Register. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00021457. Date of registration: 29 June 2020.


Subject(s)
Electric Stimulation Therapy , Gait Disorders, Neurologic , Stroke Rehabilitation , Stroke , Humans , Male , Stroke Rehabilitation/methods , Female , Middle Aged , Aged , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/rehabilitation , Electric Stimulation Therapy/methods , Stroke/complications , Stroke/physiopathology , Gait/physiology , Reflex/physiology , Adult
4.
J Neurophysiol ; 131(6): 997-1013, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38691528

ABSTRACT

During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.


Subject(s)
Forelimb , Hindlimb , Locomotion , Muscle, Skeletal , Reflex , Spinal Cord Injuries , Animals , Cats , Hindlimb/physiology , Forelimb/physiology , Reflex/physiology , Locomotion/physiology , Muscle, Skeletal/physiology , Spinal Cord Injuries/physiopathology , Movement/physiology , Female , Male , Skin/innervation
5.
Neuron ; 112(9): 1375-1378, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38697019

ABSTRACT

Animal models are instrumental to understanding the mechanisms underlying autism spectrum disorder, yet translating human behavioral phenotypes remains challenging. Wang et al. leverage a conserved sensorimotor reflex to elucidate synaptic deficits in Scn2a haploinsufficiency and pilot novel rescue strategies.


Subject(s)
Autism Spectrum Disorder , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/genetics , Humans , Animals , Reflex/physiology , Disease Models, Animal
6.
Sci Robot ; 9(90): eadl0085, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809994

ABSTRACT

Sensory feedback for prosthesis control is typically based on encoding sensory information in specific types of sensory stimuli that the users interpret to adjust the control of the prosthesis. However, in physiological conditions, the afferent feedback received from peripheral nerves is not only processed consciously but also modulates spinal reflex loops that contribute to the neural information driving muscles. Spinal pathways are relevant for sensory-motor integration, but they are commonly not leveraged for prosthesis control. We propose an approach to improve sensory-motor integration for prosthesis control based on modulating the excitability of spinal circuits through the vibration of tendons in a closed loop with muscle activity. We measured muscle signals in healthy participants and amputees during different motor tasks, and we closed the loop by applying vibration on tendons connected to the muscles, which modulated the excitability of motor neurons. The control signals to the prosthesis were thus the combination of voluntary control and additional spinal reflex inputs induced by tendon vibration. Results showed that closed-loop tendon vibration was able to modulate the neural drive to the muscles. When closed-loop tendon vibration was used, participants could achieve similar or better control performance in interfaces using muscle activation than without stimulation. Stimulation could even improve prosthetic grasping in amputees. Overall, our results indicate that closed-loop tendon vibration can integrate spinal reflex pathways in the myocontrol system and open the possibility of incorporating natural feedback loops in prosthesis control.


Subject(s)
Amputees , Artificial Limbs , Feedback, Sensory , Hand , Muscle, Skeletal , Prosthesis Design , Reflex , Vibration , Humans , Adult , Hand/physiology , Male , Female , Feedback, Sensory/physiology , Reflex/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Electromyography , Tendons/physiology , Motor Neurons/physiology , Middle Aged , Hand Strength/physiology , Young Adult
9.
J Appl Physiol (1985) ; 136(6): 1468-1477, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38601996

ABSTRACT

Acute exposure to hypoxia increases postural sway, but the underlying neurophysiological factors are unclear. Golgi tendon organs (GTOs), located within the musculotendinous junction (MTJ), provide inhibitory signals to plantar flexor muscles that are important for balance control; however, it is uncertain if GTO function is influenced by hypoxia. The aim of this study was to determine how normobaric hypoxia influences lower limb tendon-evoked inhibitory reflexes during upright stance. We hypothesized that tendon-evoked reflex area and duration would decrease during hypoxia, indicating less inhibition of postural muscles compared with normoxia. At baseline (BL; 0.21 fraction of inspired oxygen, FIO2) and at ∼2 (H2) and 4 (H4) h of normobaric hypoxia (0.11 FIO2) in a normobaric hypoxic chamber, 16 healthy participants received electrical musculotendinous stimulation (MTstim) to the MTJ of the left Achilles tendon. The MTstim was delivered as two sets of 50 stimuli while the participant stood on a force plate with their feet together. Tendon-evoked inhibitory reflexes were recorded from the surface electromyogram of the ipsilateral medial gastrocnemius, and center of pressure (CoP) variables were recorded from the force plate. Normobaric hypoxia increased CoP velocity (P ≤ 0.002) but not CoP standard deviation (P ≥ 0.12). Compared with BL, normobaric hypoxia reduced tendon-evoked inhibitory reflex area by 45% at H2 and 53% at H4 (P ≤ 0.002). In contrast, reflex duration was unchanged during hypoxia. The reduced inhibitory feedback from the GTO pathway could likely play a role in the increased postural sway observed during acute exposure to hypoxia.NEW & NOTEWORTHY The Ib pathway arising from the Golgi tendon organ provides inhibitory signals onto motor neuron pools that modifies force and, hence, postural control. Although hypoxia influences standing balance (increases sway), the underlying mechanisms have yet to be unraveled. Our study identified that tendon-evoked inhibition onto a plantar flexor motoneuron pool is reduced by acute exposure to normobaric hypoxia. This reduction of inhibition may contribute to the hypoxia-related increase in postural sway.


Subject(s)
Achilles Tendon , Hypoxia , Muscle, Skeletal , Reflex , Humans , Male , Hypoxia/physiopathology , Achilles Tendon/physiology , Achilles Tendon/physiopathology , Adult , Reflex/physiology , Female , Muscle, Skeletal/physiology , Young Adult , Electromyography/methods , Postural Balance/physiology , Electric Stimulation/methods
10.
Int J Psychophysiol ; 199: 112340, 2024 May.
Article in English | MEDLINE | ID: mdl-38574820

ABSTRACT

Sokolov described both phasic and tonic aspects of the Orienting Reflex (OR), but subsequent research and theory development has focussed primarily on the phasic OR at the expense of the tonic OR. The present study used prestimulus skin conductance level (SCL) during a dishabituation paradigm to model the tonic OR, examining its amplitude patterning over repeated standard stimulus presentations and a change stimulus. We expected sensitisation (increased amplitude) following the initial and change trials, and habituation (decrement) over the intervening trials. Prestimulus EEG alpha level was explored as a potential central measure of the tonic OR (as an inverse correlate), examining its pattern over stimulus repetition and change in relation to the SCL model. We presented a habituation series of innocuous auditory stimuli to two groups (each N = 20) at different ISIs (Long 13-15 s and Short 5-7 s) and recorded electrodermal and EEG data during two counterbalanced conditions; Indifferent: no task requirements; Significant: silent counting. Across groups and conditions, prestimulus SCLs and alpha amplitudes generally showed the expected trials patterns, confirming our main hypotheses. Findings have important implications for including the assessment of Sokolov's tonic OR in modelling central and autonomic nervous system interactions of fundamental attention and learning processes.


Subject(s)
Galvanic Skin Response , Habituation, Psychophysiologic , Humans , Habituation, Psychophysiologic/physiology , Orientation/physiology , Reflex/physiology , Attention/physiology , Acoustic Stimulation
11.
Science ; 384(6693): 269-270, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38669581

ABSTRACT

Epithelial cells in the larynx and trachea sense harmful cues and trigger protective reflexes.


Subject(s)
Larynx , Trachea , Humans , Trachea/cytology , Trachea/physiology , Larynx/physiology , Animals , Epithelial Cells/physiology , Epithelial Cells/cytology , Respiratory Mucosa/physiology , Respiratory Mucosa/cytology , Reflex/physiology
12.
Physiol Behav ; 280: 114550, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38614416

ABSTRACT

Neuroinflammation in the early postnatal period can disturb trajectories of the completion of normal brain development and can lead to mental illnesses, such as depression, anxiety disorders, and personality disorders later in life. In our study, we focused on evaluating short- and long-term effects of neonatal inflammation induced by lipopolysaccharide, poly(I:C), or their combination in female and male C57BL/6 and BTBR mice. We chose the BTBR strain as potentially more susceptible to neonatal inflammation because these mice have behavioral, neuroanatomical, and physiological features of autism spectrum disorders, an abnormal immune response, and several structural aberrations in the brain. Our results indicated that BTBR mice are more sensitive to the influence of the neonatal immune activation (NIA) on the formation of neonatal reflexes than C57BL/6 mice are. In these experiments, the injection of lipopolysaccharide had an effect on the formation of the cliff aversion reflex in female BTBR mice. Nonetheless, NIA had no delayed effects on either social behavior or anxiety-like behavior in juvenile and adolescent BTBR and C57BL/6 mice. Altogether, our data show that NIA has mimetic-, age-, and strain-dependent effects on the development of neonatal reflexes and on exploratory activity in BTBR and C57BL/6 mice.


Subject(s)
Animals, Newborn , Inflammation , Lipopolysaccharides , Mice, Inbred C57BL , Poly I-C , Animals , Female , Lipopolysaccharides/pharmacology , Male , Mice , Inflammation/chemically induced , Poly I-C/pharmacology , Anxiety/chemically induced , Social Behavior , Disease Models, Animal , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Behavior, Animal/drug effects , Behavior, Animal/physiology , Reflex/physiology , Reflex/drug effects
13.
J Physiol ; 602(9): 1881, 2024 May.
Article in English | MEDLINE | ID: mdl-38602708
14.
Clin Neurophysiol ; 162: 141-150, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38631074

ABSTRACT

OBJECTIVE: The laryngeal adductor reflex (LAR) is vital for airway protection and can be electrophysiologically obtained under intravenous general anesthesia (IGA). This makes the electrophysiologic LAR (eLAR) an important tool for monitoring of the vagus nerves and relevant brainstem circuitry during high-risk surgeries. We investigated the intra-class variability of normal and expected abnormal eLAR. METHODS: Repeated measures of contralateral R1 (cR1) were performed under IGA in 58 patients. Data on presence/absence of cR2 and potential confounders were also collected. Review of neuroimaging, pathology and clinical exam, allowed classification into normal and expected abnormal eLAR groups. Using univariate and multivariate analysis we studied the variability of cR1 parameters and their differences between the two groups. RESULTS: In both groups, cR1 latencies had coefficients of variation of <2%. In the abnormal group, cR1 had longer latencies, required higher activation currents and was more frequently desynchronized and unsustained; cR2 was more frequently absent. CONCLUSIONS: cR1 latencies show high analytical precision for measurements. Delayed onset, difficult to elicit, desynchronized and unsustained cR1, and absence of cR2 signal an abnormal eLAR. SIGNIFICANCE: Understanding the variability and behavior of normal and abnormal eLAR under IGA can aid in the interpretation of its changes during monitoring.


Subject(s)
Reflex , Humans , Male , Female , Middle Aged , Aged , Reflex/physiology , Adult , Laryngeal Muscles/physiopathology , Laryngeal Muscles/physiology , Electromyography/methods
15.
Neurourol Urodyn ; 43(5): 1230-1237, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38567649

ABSTRACT

OBJECTIVE: Functional MRI (fMRI) can be employed to assess neuronal activity in the central nervous system. However, investigating the spinal cord using fMRI poses several technical difficulties. Enhancing the fMRI signal intensity in the spinal cord can improve the visualization and analysis of different neural pathways, particularly those involved in bladder function. The bulbocavernosus reflex (BCR) is an excellent method for evaluating the integrity of the sacral spinal cord. Instead of stimulating the glans penis or clitoris, the BCR can be simulated comfortably by tapping the suprapubic region. In this study, we explain the necessity and development of a device to elicit the simulated BCR (sBCR) via suprapubic tapping while conducting an fMRI scan. METHODS: The device was successfully tested on a group of 20 healthy individuals. Two stimulation task block protocols were administered (empty vs. full bladder). Each block consisted of 40 s of suprapubic tapping followed by 40 s of rest, and the entire sequence was repeated four times. RESULTS: Our device can reliably and consistently elicit sBCR noninvasively as demonstrated by electromyographic recording of pelvic muscles and anal winking. Participants did note mild to moderate discomfort and urge to void during the full bladder task. CONCLUSION: Our device demonstrates an efficacious approach to elicit sBCR within an MRI bore to assess sacral spinal cord functional activity without generating any significant motion artifacts. SIGNIFICANCE: This device can explore the mechanisms and processes controlling urinary, digestive, or sexual function within this region in humans.


Subject(s)
Magnetic Resonance Imaging , Reflex , Spinal Cord , Humans , Magnetic Resonance Imaging/instrumentation , Male , Adult , Female , Spinal Cord/physiology , Spinal Cord/diagnostic imaging , Reflex/physiology , Urinary Bladder/physiology , Urinary Bladder/diagnostic imaging , Electromyography/instrumentation , Young Adult , Physical Stimulation/instrumentation , Middle Aged
16.
Science ; 384(6693): 295-301, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38669574

ABSTRACT

Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea, and larynx remain largely unknown. In this work, we show that murine NE cells in these compartments have distinct biophysical properties but share sensitivity to two commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing adenosine 5'-triphosphate (ATP) to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers the broad molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating protective responses.


Subject(s)
Adenosine Triphosphate , Larynx , Neuroendocrine Cells , Reflex , Trachea , Animals , Mice , Neuroendocrine Cells/metabolism , Larynx/physiology , Adenosine Triphosphate/metabolism , Reflex/physiology , Trachea/innervation , Trachea/cytology , Deglutition , Lung/physiology , Exhalation/physiology , Water/metabolism , Sensory Receptor Cells/physiology , Mice, Inbred C57BL
18.
J Physiol ; 602(9): 1987-2017, 2024 May.
Article in English | MEDLINE | ID: mdl-38593215

ABSTRACT

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.


Subject(s)
Hindlimb , Locomotion , Muscle, Skeletal , Reflex , Spinal Cord Injuries , Animals , Cats , Hindlimb/innervation , Hindlimb/physiology , Hindlimb/physiopathology , Male , Female , Spinal Cord Injuries/physiopathology , Reflex/physiology , Locomotion/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Skin/innervation , Thoracic Vertebrae , Forelimb/physiopathology , Forelimb/physiology , Electric Stimulation
19.
Eur J Appl Physiol ; 124(7): 2183-2192, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38441687

ABSTRACT

Cardiovascular responses to diving are characterized by two opposing responses: tachycardia resulting from exercise and bradycardia resulting from the apnea. The convergence of bradycardia and tachycardia may determine the cardiovascular responses to diving. The purpose of this study was to investigate the interaction of breath holding and muscle mechanoreflex on cardiovascular responses in breath-hold divers (BHDs) and non-BHDs. We compared the cardiovascular responses to combined apnea and the mechanoreflex in BHDs and non-BHDs. All participants undertook three trials-apnea, passive leg cycling (PLC), and combined trials-for 30 s after rest. Cardiovascular variables were measured continuously. Nine BHD (male:female, 4:5; [means ± SD] age, 35 ± 6 years; height, 168.6 ± 4.6 cm; body mass, 58.4 ± 5.9 kg) and eight non-BHD (male:female, 4:4; [means ± SD] age, 35 ± 7 years; height, 163.9 ± 9.1 cm; body mass, 55.6 ± 7.2 kg) participants were included. Compared to the resting baseline, heart rate (HR) and cardiac output (CO) significantly decreased during the combined trial in the BHD group, while they significantly increased during the combined trials in the non-BHD group (P < 0.05). Changes in the HR and CO were significantly lower in the BHD group than in the non-BHD group in the combined trial (P < 0.05). These results suggest that bradycardia with apnea in BHDs is prioritized over tachycardia with the mechanoreflex, whereas that in non-BHDs is not. This finding implies that diving training changes the interaction between apnea and the mechanoreflex in cardiovascular control.


Subject(s)
Breath Holding , Diving , Heart Rate , Humans , Male , Female , Adult , Diving/physiology , Heart Rate/physiology , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Apnea/physiopathology , Reflex/physiology , Cardiac Output/physiology , Diving Reflex/physiology , Blood Pressure/physiology
20.
J Appl Physiol (1985) ; 136(5): 1226-1237, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38545661

ABSTRACT

Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult University of California Davis (UCD)-T2DM (n = 8) and healthy Sprague-Dawley (n = 8) rats. Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as means ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: Δ32 ± 13 mmHg and After: Δ18 ± 8 mmHg; P = 0.004) and blood pressor index (BPi) (Before: Δ683 ± 324 mmHg·s and After: Δ361 ± 222 mmHg·s; P = 0.006), but not HR (Before: Δ23 ± 8 beats/min and After Δ19 ± 10 beats/min; P = 0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR, or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E2 in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM.NEW & NOTEWORTHY We compared the pressor and cardioaccelerator responses to static muscle contraction before and after inhibition of cyclooxygenase (COX) activity within the contracting hindlimb in decerebrate, unanesthetized type 2 diabetic mellitus (T2DM) and healthy rats. The pressor responses to muscle contraction were attenuated after peripheral inhibition of COX activity in T2DM but not in healthy rats. We concluded that COX products partially contribute to the exaggerated pressor reflex in those with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Muscle Contraction , Muscle, Skeletal , Reflex , Animals , Male , Rats , Arterial Pressure/physiology , Blood Pressure/physiology , Blood Pressure/drug effects , Cyclooxygenase Inhibitors/pharmacology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/metabolism , Heart Rate/physiology , Heart Rate/drug effects , Indomethacin/pharmacology , Muscle Contraction/physiology , Muscle, Skeletal/physiopathology , Physical Conditioning, Animal/physiology , Prostaglandin-Endoperoxide Synthases/metabolism , Rats, Sprague-Dawley , Reflex/physiology
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