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Cardiovascular Research Oct 2023The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the...
AIMS
The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the development of cardiovascular responses during exercise, however, the patterns of changes in the activity of the two autonomic limbs, and their functional interactions in orchestrating physiological responses during exercise, are not fully understood. The aim of this study was to characterize changes in vagal parasympathetic drive in response to exercise and exercise training by directly recording the electrical activity of vagal preganglionic neurons in experimental animals (rats).
METHODS AND RESULTS
Single unit recordings were made using carbon-fibre microelectrodes from the populations of vagal preganglionic neurons of the nucleus ambiguus (NA) and the dorsal vagal motor nucleus of the brainstem. It was found that (i) vagal preganglionic neurons of the NA and the dorsal vagal motor nucleus are strongly activated during bouts of acute exercise, and (ii) exercise training markedly increases the resting activity of both populations of vagal preganglionic neurons and augments the excitatory responses of NA neurons during exercise.
CONCLUSIONS
These data show that central vagal drive increases during exercise and provide the first direct neurophysiological evidence that exercise training increases vagal tone. The data argue against the notion of exercise-induced central vagal withdrawal during exercise. We propose that robust increases in the activity of vagal preganglionic neurons during bouts of exercise underlie activity-dependent plasticity, leading to higher resting vagal tone that confers multiple health benefits associated with regular exercise.
Topics: Rats; Animals; Autonomic Fibers, Preganglionic; Vagus Nerve; Heart; Neurons; Medulla Oblongata
PubMed: 37516977
DOI: 10.1093/cvr/cvad115 -
Neuroscience Letters Mar 2023Disturbances that threaten homeostasis elicit activation of the sympathetic nervous system (SNS) and the adrenal medulla. The effectors discharge as a unit to drive...
Disturbances that threaten homeostasis elicit activation of the sympathetic nervous system (SNS) and the adrenal medulla. The effectors discharge as a unit to drive global and immediate changes in whole-body physiology. Descending sympathetic information is conveyed to the adrenal medulla via preganglionic splanchnic fibers. These fibers pass into the gland and synapse onto chromaffin cells, which synthesize, store, and secrete catecholamines and vasoactive peptides. While the importance of the sympatho-adrenal branch of the autonomic nervous system has been appreciated for many decades, the mechanisms underlying transmission between presynaptic splanchnic neurons and postsynaptic chromaffin cells have remained obscure. In contrast to chromaffin cells, which have enjoyed sustained attention as a model system for exocytosis, even the Ca sensors that are expressed within splanchnic terminals have not yet been identified. This study shows that a ubiquitous Ca-binding protein, synaptotagmin-7 (Syt7), is expressed within the fibers that innervate the adrenal medulla, and that its absence can alter synaptic transmission in the preganglionic terminals of chromaffin cells. The prevailing impact in synapses that lack Syt7 is a decrease in synaptic strength and neuronal short-term plasticity. Evoked excitatory postsynaptic currents (EPSCs) in Syt7 KO preganglionic terminals are smaller in amplitude than in wild-type synapses stimulated in an identical manner. Splanchnic inputs also display robust short-term presynaptic facilitation, which is compromised in the absence of Syt7. These data reveal, for the first time, a role for any synaptotagmin at the splanchnic-chromaffin cell synapse. They also suggest that Syt7 has actions at synaptic terminals that are conserved across central and peripheral branches of the nervous system.
Topics: Acetylcholine; Synaptotagmins; Splanchnic Nerves; Chromaffin Cells; Adrenal Medulla; Synapses
PubMed: 36796621
DOI: 10.1016/j.neulet.2023.137129 -
Current Medical Science Feb 2023The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is...
OBJECTIVE
The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is specifically expressed on nerves, especially on pre-ganglionic sensory fibers. This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.
METHODS
The Sprague-Dawley rats were divided randomly into three groups: sham group-myocardial infarction group, and myocardial infarction with gefapixant treatment group. Myocardial infarction was induced by left anterior descending branch ligation. The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers. Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III. The sympathetic innervation was detected by norepinephrine concentration (pg/mL), in-vivo electrophysiology, and typical sympathetic biomarkers. Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology, quantitative realtime PCR (qPCR) and Western blotting.
RESULTS
It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio. Furthermore, gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS, and decreased LVIDd and LVIDs. The expression levels of collagen I and collagen III, and TNF-α were all decreased by P2X3 inhibition. Mechanistically, the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 (NLRP3) inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β (IL-1β) and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation.
CONCLUSION
It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance, cardiac dysfunction, and remodeling possibly via inactivating NLRP3 inflammasome.
Topics: Rats; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Myocardial Infarction; Collagen; Biomarkers
PubMed: 36622629
DOI: 10.1007/s11596-022-2658-5 -
Journal of Cardiovascular Development... Nov 2022Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after...
Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after crossing the preganglionic fibers of the vagus nerve has not been enough studied. The aim of our study was to assess the effect of physical training on the morphological parameters of the parasympathetic atrial ganglia and autonomic regulation of heart rate after right- and left-sided vagotomy in rats. Morphometric characteristics of the right atrial ganglia were evaluated using an immunohistochemical method after a study that included a three-time assessment of heart rate variability. It was found that right-sided vagotomy leads to both an increase in the volume of ganglion and autonomic dysfunction. No significant change in the number of nerve cells was found in animals with false and left-sided vagotomy while maintaining preganglionic innervation after the physical training, whereas exercises led to a decrease in the volume of nerve tissue of rats with right-sided denervation. It was also found that in animals with preserved vagal innervation, the volume of atrial ganglion tissue correlates with overall heart rate variability and a normalized parasympathetic component. Therefore, a positive effect from regular physical activity on parasympathetic regulation can be expected only if preganglionic vagal influence is preserved.
PubMed: 36421926
DOI: 10.3390/jcdd9110391 -
The Egyptian Heart Journal : (EHJ) :... Sep 2022Acute cervical spinal trauma may lead to cardiac effects by influencing cardiac sympathetic preganglionic fibers. Some of these effects, which are vital, may occur in...
BACKGROUND
Acute cervical spinal trauma may lead to cardiac effects by influencing cardiac sympathetic preganglionic fibers. Some of these effects, which are vital, may occur in ECG.
CASE PRESENTATION
A 52-year-old female patient admitted to the emergency department with acute traumatic spondylolisthesis at C6-C7 level and paraplegia. Positive QRS complex, ST segment depressions and prolongation of QTc interval were observed on ECG according to sudden autonomic disruption because of sympathetic nerve compression. It was mentioned that changes in QRS complex axis was normal which was dependent to the ECG display format of Cabrera sequence used differently from the classical system. After surgical correction, evident ST depressions were recovered and QTc intervalwas narrowed but still prolonged in control ECG.
CONCLUSIONS
Autonomic dysfunction can lead to extraordinary electrocardiographic presentation including widespread ST depressions with prolonged QTc interval. However, when evaluating the changes in the ECG, attention should be paid to ECG display format to avoid errors in interpretation.
PubMed: 36057680
DOI: 10.1186/s43044-022-00301-w -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2023Along with well-known data on the neurochemical mechanisms of nociceptor activation, there are still no clear data regarding changes in the cellular composition and...
Along with well-known data on the neurochemical mechanisms of nociceptor activation, there are still no clear data regarding changes in the cellular composition and morphological characteristics of spinal preganglionic neurons (SPN) after capsaicin treatment. The mechanism of capsaicin toxicity differs in developing and mature nerve cells. This study aimed to determine the number of SPN in the autonomic nuclei on spinal cord (SC) sections and their cross-sectional area, the localization, percentage, and profile area of SPN containing neuronal nitric oxide synthase (nNOS) and calbindin (CB) in the thoracic SC of rats of different ages (from birth to 1-year-old) after capsaicin treatment. Neonatal capsaicin treatment generally decreased the cross-sectional area of the SPN pericarya. However, the cross-sectional area of the CB-immunoreactive (IR) SPN increased in the central autonomic area in rats aged 10-30 days old after capsaicin treatment. The number of SPN decreased only in the central autonomic area of rats aged <20 days. The proportion of nNOS-IR neurons remained steady and did not change during development. The cross-sectional area of nNOS-IR SPN in capsaicin-treated rats was less than that in control rats. The results obtained will promote further studies on the mechanisms of sensory processing in the SC and the development of the sympathetic nervous system.
Topics: Rats; Animals; Nitric Oxide Synthase Type I; Capsaicin; Calbindins; Neurons; Sympathetic Nervous System; Spinal Cord; Autonomic Fibers, Preganglionic
PubMed: 35717590
DOI: 10.1002/ar.25012 -
Neurotrauma Reports 2022Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive...
Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive production/passage of urine (polyuria) has been understudied. Pre-clinical animal studies investigating SCI-induced polyuria have been carried out in T8-T10 spinal-level contusive injuries, which directly impacts both supraspinal sympathetic inputs to the spinal circuitry mediating kidney function as well as local networks including pre-ganglionic sympathetic fibers to the kidney. The current study utilizes a higher-level (T3) contusion to narrow the potential source(s) of damage that induce(s) polyuria. Metabolic cage 24-h urine collections demonstrated that, starting 1 week post-SCI and lasting chronically through 6 weeks post-SCI, T3 contused adult male rats had a significant increase in void volume relative to pre-injury and surgical sham controls. Subsequent examination of previously identified biomarkers revealed levels reflecting the presence of polyuria. For example, urine atrial natriuretic peptide levels were significantly increased at 6 weeks post-SCI compared to baseline, and serum arginine vasopressin (AVP) levels were significantly decreased. Further, there was a significant decrease post-injury relative to shams in the number of AVP-labeled cells within the suprachiasmatic nucleus, a hypothalamic region responsible for significant disruptions of circadian rhythmicity post-SCI, including loss of the diurnal variation of AVP production, which clinical studies have identified as contributing to the emergence of nocturia after SCI. Together, the current results demonstrate that SCI-induced polyuria is present after a T3-level SCI, indicating that damage of descending supraspinal circuitries precipitates dysfunction of homeostatic mechanisms involved in salt and water balance.
PubMed: 35558732
DOI: 10.1089/neur.2022.0014