The Journal of Physiology最新文献

{"title":"Commonality and heterogeneity of pacemaker mechanisms in the male reproductive organs","authors":"Hikaru Hashitani, Mitsue Takeya, Dirk F. van Helden","doi":"10.1113/jp284756","DOIUrl":"https://doi.org/10.1113/jp284756","url":null,"abstract":"During emission, the first phase of ejaculation, smooth muscle in organs of the male reproductive tract (MRT) vigorously contract upon sympathetic nerve excitation to expel semen consisting of sperm and seminal plasma. During inter-ejaculation phases, the epididymis, seminal vesicles and prostate undergo spontaneous phasic contractions (SPCs), this transporting and maintaining the quality of sperm and seminal plasma. Recent studies have revealed platelet-derived growth factor receptor α-expressing (PDGFRα⁺) subepithelial interstitial cells in seminal vesicles subserve the role of pacemaker cells that electrically drive SPCs in this organ. PDGFRα⁺ smooth muscle cells in the epididymis also appear to function as pacemaker cells implicating PDGFRα as a potential signature molecule in MRT pacemaking. The dominant mechanism driving pacemaking in these organs is the cytosolic Ca²⁺ oscillator. This operates through entrainment of the release-refill cycle of Ca²⁺ stores, the released Ca²⁺ ions opening Ca²⁺-activated chloride channels, including in some cases ANO1 (TMEM16A), with the resultant pacemaker potential activating L-type voltage-dependent Ca²⁺ channels in the smooth muscle causing contraction (viz. SPCs). A second pacemaker mechanism, namely the membrane oscillator also has a role in specific cases. Further investigations into the commonality and heterogeneity of MRT pacemakers will open an avenue for understanding the pathogenesis of male infertility associated with deterioration of seminal plasma.","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":"137 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related difference in sympathetic chemoreflex response: does it matter in clinical disease?","authors":"Francesco Gentile, Michele Emdin, Claudio Passino, Alberto Giannoni","doi":"10.1113/JP283643","DOIUrl":"https://doi.org/10.1113/JP283643","url":null,"abstract":"We read with great interest the work of Sayegh et al. (2022) recently published in The Journal of Physiology. In their elegant study, the authors aimed to assess, for the first time, the sex-related difference in the respiratory and sympathetic neurocirculatory responses (estimated through muscle sympathetic nerve activity, MSNA) to central, peripheral and combined chemoreflex activation in 10 male and 10 female healthy volunteers. The authors confirm that ventilatory and adrenergic responses to chemoreflex activation may be partially independent within the same individual. Although both responses are initiated at similar recruitment thresholds, the sympathetic response to chemoreflex stimulation cannot be predicted from the ventilatory response, as suggested by Keir and co-workers (2019). Further, the study shows a greater total MSNA response to hypercapnia (on either hyperoxic or hypoxic background) in women, as compared to men, despite an attenuated ventilatory response to hypercapnia (Sayegh et al., 2022). The greater sympathetic response to central chemoreflex activation in women unveils potential","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4247-4248"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40615691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of respiratory loading on left-ventricular function in cervical spinal cord injury.","authors":"Cameron M Gee,&nbsp;Alexandra M Williams,&nbsp;Carli M Peters,&nbsp;Neil D Eves,&nbsp;Andrew W Sheel,&nbsp;Christopher R West","doi":"10.1113/JP282717","DOIUrl":"https://doi.org/10.1113/JP282717","url":null,"abstract":"<p><p>Cervical spinal cord injury (C-SCI) negatively impacts cardiac and respiratory function. As the heart and lungs are linked via the pulmonary circuit these systems are interdependent. Here, we utilized inspiratory and expiratory loading to assess whether augmenting the respiratory pump improves left-ventricular (LV) filling and output in individuals with motor-complete C-SCI. We hypothesized LV end-diastolic volume (LVEDV) would increase and decrease with inspiratory and expiratory loading, respectively. Participants (C-SCI: 7M/1F, 35 ± 7 years; able-bodied: 7M/1F, 32 ± 6 years) were assessed under five conditions during 45° head-up tilt; unloaded, inspiratory loading with -10 and -20 cmH₂ O oesophageal pressure (P_oes ) on inspiration, and expiratory loading with +10 and +20 cmH₂ O P_oes on expiration. An oesophageal balloon catheter monitored P_oes , and LV structure and function were assessed by echocardiography. In C-SCI only, (1) +20 cmH₂ O reduced LVEDV vs. unloaded (81 ± 15 vs. 88 ± 11 ml, P = 0.006); (2) heart rate was higher during +20 cmH₂ O compared to unloaded (P = 0.001) and +10 cmH₂ O (P = 0.002); (3) cardiac output was higher during +20 cmH₂ O than unloaded (P = 0.002); and (4) end-expiratory lung volume was higher during +20 cmH₂ O vs. unloaded (63 ± 10 vs. 55 ± 13% total lung capacity, P = 0.003) but was unaffected by inspiratory loading. In both groups, -10 and -20 cmH₂ O had no significant effect on LVEDV. These findings suggest greater expiratory positive pressure acutely impairs LV filling in C-SCI, potentially via impaired venous return, mediastinal constraint and/or direct ventricular interaction subsequent to dynamic hyperinflation. Inspiratory loading did not significantly improve LV function in C-SCI and neither inspiratory nor expiratory loading affected cardiac function or lung volumes in able-bodied participants. KEY POINTS: Cervical spinal cord injury (C-SCI) alters both the cardiac and the respiratory system, but little is known about how these systems interact following injury. Here, we manipulated inspiratory or expiratory intrathoracic pressure (ITP) to mechanistically test the role of the respiratory pump in circulatory function in highly trained individuals with C-SCI and an able-bodied reference group. In individuals with C-SCI, greater ITP during expiratory loading caused dynamic hyperinflation that was associated with impaired left-ventricular filling. More negative ITP during inspiratory loading did not significantly alter left-ventricular volumes in either group. Interventions that prevent dynamic hyperinflation and/or enhance the ability to generate expiratory pressures may help preserve left-ventricular filling in individuals with C-SCI.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4105-4118"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40398282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ketogenic diet prevents steatosis and insulin resistance by reducing lipogenesis, diacylglycerol accumulation and protein kinase C activity in male rat liver.","authors":"Shailee Jani,&nbsp;Daniel Da Eira,&nbsp;Mateja Stefanovic,&nbsp;Rolando B Ceddia","doi":"10.1113/JP283552","DOIUrl":"https://doi.org/10.1113/JP283552","url":null,"abstract":"<p><p>Obesity-associated insulin resistance plays a major role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause NAFLD. In recent years, the ketogenic diet (KD) has emerged as an effective non-pharmacological intervention for the treatment of NAFLD and other obesity-related metabolic disorders. What remains undetermined is how the KD affects DAG and ceramide content and insulin sensitivity in the liver. Thus, this research was designed to assess these variables, as well as glucose and fat metabolism and markers of inflammation in livers of rats exposed for 8 weeks to one of the following diets: standard chow (SC), obesogenic high-fat, sucrose-enriched diet (HFS) or a KD. Despite having a higher fat content than the HFS diet, the KD did not cause steatosis and preserved hepatic insulin signalling. The KD reduced DAG content and protein kinase C-ε activity, but markedly increased liver ceramide content. However, whereas the KD increased ceramide synthase 2 (CerS2) expression, it suppressed CerS6 expression, an effect that promoted the production of beneficial very long-chain ceramides instead of harmful long-chain ceramides. The KD also enhanced the liver expression of key genes involved in mitochondrial biogenesis and fatty acid oxidation (Pgc-1α and Fgf21), suppressed inflammatory genes (Tnfα, Nf-kb, Tlr4 and Il6), and shifted substrate away from de novo lipogenesis. Thus, through multiple mechanisms the KD exerted anti-steatogenic and insulin-sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD. KEY POINTS: The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause insulin resistance and non-alcoholic fatty liver disease (NAFLD). This study provides evidence that a ketogenic diet (KD) rich in fat and devoid of carbohydrate reduced DAG content and preserved insulin signalling in the liver. The KD shifted metabolism away from lipogenesis by enhancing genes involved in mitochondrial biogenesis and fatty acid oxidations in the liver. The KD also promoted the production of beneficial very long-chain ceramides instead of potentially harmful long-chain ceramides. Through multiple mechanisms, the KD exerted anti-steatogenic and insulin-sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4137-4151"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40619111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variation in HIF-2α attenuates ventilatory sensitivity and carotid body growth in chronic hypoxia in high-altitude deer mice.","authors":"Catherine M Ivy, Jonathan P Velotta, Zachary A Cheviron, Graham R Scott","doi":"10.1113/JP282798","DOIUrl":"10.1113/JP282798","url":null,"abstract":"<p><p>The gene encoding HIF-2α, Epas1, has experienced a history of natural selection in many high-altitude taxa, but the functional role of mutations in this gene is still poorly understood. We investigated the influence of the high-altitude variant of Epas1 in North American deer mice (Peromyscus maniculatus) on the control of breathing and carotid body growth during chronic hypoxia. We created hybrids between high- and low-altitude populations of deer mice to disrupt linkages between genetic loci so that the physiological effects of Epas1 alleles (Epas1^H and Epas1^L , respectively) could be examined on an admixed genomic background. In general, chronic hypoxia (4 weeks at 12 kPa O₂ ) enhanced ventilatory chemosensitivity (assessed as the acute ventilatory response to hypoxia), increased total ventilation and arterial O₂ saturation during progressive poikilocapnic hypoxia, and increased haematocrit and blood haemoglobin content across genotypes. However, the effects of chronic hypoxia on ventilatory chemosensitivity were attenuated in mice that were homozygous for the high-altitude Epas1 allele (Epas1^H/H ). Carotid body growth and glomus cell hyperplasia, which was strongly induced in Epas1^L/L mice in chronic hypoxia, was not observed in Epas1^H/H mice. Epas1 genotype also modulated the effects of chronic hypoxia on metabolism and body temperature depression in hypoxia, but had no effects on haematological traits. These findings confirm the important role of HIF-2α in modulating ventilatory sensitivity and carotid body growth in chronic hypoxia, and show that genetic variation in Epas1 is responsible for evolved changes in the control of breathing and metabolism in high-altitude deer mice. KEY POINTS: High-altitude natives of many species have experienced natural selection on the gene encoding HIF-2α, Epas1, including high-altitude populations of deer mice. HIF-2α regulates ventilation and carotid body growth in hypoxia, and so the genetic variants in Epas1 in high-altitude natives may underlie evolved changes in control of breathing. Deer mice from controlled crosses between high- and low-altitude populations were used to examine the effects of Epas1 genotype on an admixed genomic background. The high-altitude variant was associated with reduced ventilatory chemosensitivity and carotid body growth in chronic hypoxia, but had no effects on haematology. The results help us better understand the genetic basis for the unique physiological phenotype of high-altitude natives.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4207-4225"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kappa opioids inhibit the GABA/glycine terminals of rostral ventromedial medulla projections in the superficial dorsal horn of the spinal cord.","authors":"Yo Otsu,&nbsp;Karin R Aubrey","doi":"10.1113/JP283021","DOIUrl":"https://doi.org/10.1113/JP283021","url":null,"abstract":"<p><p>Descending projections from neurons in the rostral ventromedial medulla (RVM) make synapses within the superficial dorsal horn (SDH) of the spinal cord that are involved in the modulation of nociception, the development of chronic pain and itch, and an important analgesic target for opioids. This projection is primarily inhibitory, but the relative contribution of GABAergic and glycinergic transmission is unknown and there is limited knowledge about the SDH neurons targeted. Additionally, the details of how spinal opioids mediate analgesia remain unclear, and no study has investigated the opioid modulation of this synapse. We address this using ex vivo optogenetic stimulation of RVM fibres in conjunction with whole-cell patch-clamp recordings from the SDH in spinal cord slices. We demonstrate that both GABAergic and glycinergic neurotransmission is employed and show that SDH target neurons have diverse morphological and electrical properties, consistent with both inhibitory and excitatory interneurons. Then, we describe a subtype of SDH neurons that has a glycine-dominant input, indicating that the quality of descending inhibition across cells is not uniform. Finally, we discovered that the kappa-opioid receptor agonist U69593 presynaptically suppressed most RVM-SDH synapses. By contrast, the mu-opioid receptor agonist DAMGO acted both pre- and postsynaptically at a subset of synapses, and the delta-opioid receptor agonist deltorphin II had little effect. These data provide important mechanistic information about a descending control pathway that regulates spinal circuits. This information is necessary to understand how sensory inputs are shaped and develop more reliable and effective alternatives to current opioid analgesics.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4187-4205"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/cd/TJP-600-4187.PMC9540474.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40622241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exertional dyspnoea in patients with mild-to-severe chronic obstructive pulmonary disease: neuromechanical mechanisms.","authors":"Matthew D James,&nbsp;Devin B Phillips,&nbsp;Sandra G Vincent,&nbsp;Sara J Abdallah,&nbsp;Adamo A Donovan,&nbsp;Juan P de-Torres,&nbsp;J Alberto Neder,&nbsp;Benjamin M Smith,&nbsp;Dennis Jensen,&nbsp;Denis E O'Donnell","doi":"10.1113/JP283252","DOIUrl":"https://doi.org/10.1113/JP283252","url":null,"abstract":"&lt;p&gt;&lt;p&gt;In patients with chronic obstructive pulmonary disease (COPD), exertional dyspnoea generally arises when there is imbalance between ventilatory demand and capacity, but the neurophysiological mechanisms are unclear. We therefore determined if disparity between elevated inspiratory neural drive (IND) and tidal volume (V&lt;sub&gt;T&lt;/sub&gt; ) responses (neuromechanical dissociation) impacted dyspnoea intensity and quality during exercise, across the COPD severity spectrum. In this two-centre, cross-sectional observational study, 89 participants with COPD divided into tertiles of FEV&lt;sub&gt;1&lt;/sub&gt; %predicted (Tertile 1 = FEV&lt;sub&gt;1&lt;/sub&gt; = 87 ± 9%, Tertile 2 = 60 ± 9%, Tertile 3 = 32 ± 8%) and 18 non-smoking controls, completed a symptom-limited cardiopulmonary exercise test (CPET) with measurement of IND by diaphragm electromyography (EMGdi (%max)). The association between increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r = 0.730, P &lt; 0.001) and not different between the four groups who showed marked heterogeneity in pulmonary gas exchange and mechanical abnormalities. Significant inspiratory constraints (tidal volume/inspiratory capacity (V&lt;sub&gt;T&lt;/sub&gt; /IC) ≥ 70%) and onset of neuromechanical dissociation (EMGdi (%max):V&lt;sub&gt;T&lt;/sub&gt; /IC &gt; 0.75) occurred at progressively lower minute ventilation ( &lt;math&gt; &lt;semantics&gt; &lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt; &lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt; &lt;mi&gt;E&lt;/mi&gt;&lt;/msub&gt; &lt;annotation&gt;${dot{V}}_{{rm{E}}}$&lt;/annotation&gt;&lt;/semantics&gt; &lt;/math&gt; ) from Control to Tertile 3. Lower resting IC meant earlier onset of neuromechanical dissociation, heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to select qualitative descriptors of 'unsatisfied inspiration'. We concluded that, regardless of marked variation in mechanical and pulmonary gas exchange abnormalities in our study sample, exertional dyspnoea intensity was linked to the magnitude of EMGdi (%max). Moreover, onset of critical inspiratory constraints and attendant neuromechanical dissociation amplified dyspnoea intensity at higher exercise intensities. Simple measurements of IC and breathing pattern during CPET provide useful insights into mechanisms of dyspnoea and exercise intolerance in individuals with COPD. KEY POINTS: Dyspnoea during exercise is a common and troublesome symptom reported by patients with chronic obstructive pulmonary disease (COPD) and is linked to an elevated inspiratory neural drive (IND). The precise mechanisms of elevated IND and dyspnoea across the continuum of airflow obstruction severity in COPD remains unclear. The present study sought to determine the mechanisms of elevated IND (by diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise testing (CPET) across the continuum of COPD severity. There was a strong association between increasing dyspnoea intensity and EMGdi (%max) during CPET across the COPD continuum despite significant heterogeneity in underlying pulmonary gas exchange and respiratory mechanical impair","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4227-4245"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40541614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory gene expression during acute high-altitude exposure.","authors":"Kathy Pham,&nbsp;Shyleen Frost,&nbsp;Keval Parikh,&nbsp;Nikhil Puvvula,&nbsp;Britney Oeung,&nbsp;Erica C Heinrich","doi":"10.1113/JP282772","DOIUrl":"https://doi.org/10.1113/JP282772","url":null,"abstract":"<p><p>The molecular signalling pathways that regulate inflammation and the response to hypoxia share significant crosstalk and appear to play major roles in high-altitude acclimatization and adaptation. Several studies demonstrate increases in circulating candidate inflammatory markers during acute high-altitude exposure, but significant gaps remain in our understanding of how inflammation and immune function change at high altitude and whether these responses contribute to high-altitude pathologies, such as acute mountain sickness. To address this, we took an unbiased transcriptomic approach, including RNA sequencing and direct digital mRNA detection with NanoString, to identify changes in the inflammatory profile of peripheral blood throughout 3 days of high-altitude acclimatization in healthy sea-level residents (n = 15; five women). Several inflammation-related genes were upregulated on the first day of high-altitude exposure, including a large increase in HMGB1 (high mobility group box 1), a damage-associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Differentially expressed genes on the first and third days of acclimatization were enriched for several inflammatory pathways, including nuclear factor-κB and Toll-like receptor (TLR) signalling. Indeed, both TLR4 and LY96, which encodes the lipopolysaccharide binding protein (MD-2), were upregulated at high altitude. Finally, FASLG and SMAD7 were associated with acute mountain sickness scores and peripheral oxygen saturation levels on the first day at high altitude, suggesting a potential role of immune regulation in response to high-altitude hypoxia. These results indicate that acute high-altitude exposure upregulates inflammatory signalling pathways and might sensitize the TLR4 signalling pathway to subsequent inflammatory stimuli. KEY POINTS: Inflammation plays a crucial role in the physiological response to hypoxia. High-altitude hypoxia exposure causes alterations in the inflammatory profile that might play an adaptive or maladaptive role in acclimatization. In this study, we characterized changes in the inflammatory profile following acute high-altitude exposure. We report upregulation of novel inflammation-related genes in the first 3 days of high-altitude exposure, which might play a role in immune system sensitization. These results provide insight into how hypoxia-induced inflammation might contribute to high-altitude pathologies and exacerbate inflammatory responses in critical illnesses associated with hypoxaemia.</p>","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"4169-4186"},"PeriodicalIF":5.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/50/23/TJP-600-4169.PMC9481729.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40536510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic plasticity of medial olivocochlear efferent system: insights and application for neurotology.","authors":"Shaun A Hanycz,&nbsp;Vishaal Sumra,&nbsp;Anshu Kashyap,&nbsp;Anthony Pokhoy","doi":"10.1113/JP283448","DOIUrl":"https://doi.org/10.1113/JP283448","url":null,"abstract":"Shaun A. Hanycz1 , Vishaal Sumra2,3, Anshu Kashyap1 and Anthony Pokhoy4 1Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada 2Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada 3Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada 4Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"3653-3655"},"PeriodicalIF":5.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40511676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-related differences in the peripheral vascular response to reflex coactivation: Fun physiology or window of opportunity?","authors":"Jacqueline K Limberg","doi":"10.1113/JP283474","DOIUrl":"https://doi.org/10.1113/JP283474","url":null,"abstract":"The carotid chemoreceptors are the body’s primary oxygen sensors. Located bilaterally at the bifurcation of the common carotid artery, they are well-situated to sense changes in arterial partial pressure of oxygen and elicit necessary reflex responses (e.g. hyperventilation). In addition to their known oxygen-sensing capabilities, the carotid chemoreceptors play an important role in the integrative cardiovascular response to exercise. Indeed, activity of the sympathetic nervous system increases with exercise and at least a portion of sympathetic vasoconstrictor tone can be attributed to the chemoreceptors. The role for the carotid chemoreceptors in the sympathetic response to exercise becomes particularly relevant in the context of clinical conditions such as hypertension, heart failure and perhaps even diabetes. In both pre-clinical models and human patients with heart failure, the contribution of the carotid chemoreceptors to sympathetic vasoconstrictor tone is evident even at rest. Inhibition of chemoreceptor activity can further improve cardiovascular regulation during exercise in heart failure (Collins et al., 2020). The mechanisms by which this may be occurring are many and include interactions between the exercise pressor reflex (i.e. mechanoand metaboreflex) and the carotid chemoreceptors (Edgell & Stickland, 2014). Thus, chemoreceptor activation in the context of exercise may potentiate cardiovascular consequences of such conditions. Notably, the metaboreflex was recently identified to contribute to enhanced peripheral vasoconstriction in patients with heart failure (Barrett-O’Keefe et al., 2018). When considered clinically, exaggerated sympathetically-mediated vasoconstriction in the context of exercise is not limited to the skeletal muscle circulation and has similarly been observed at the level of the kidney. Although this work has been shown to provide comparable results across species (e.g. dogs, humans), less is known regarding the translation of findings across sexes. A lack of understanding of sex-related differences in reflex interactions is primarily a result of the tendency of prior work to include only males or a very small proportion of females. As a result, sex-related differences have only recently been identified and remain poorly described in clinical cohorts. In the most recent issue of The Journal of Physiology, Wan et al. (2022) tested the hypothesis that reflex interactions between the muscle mechanoreflex (passive limb movement) and chemoreflex (hypoxia, hypercapnia) would restrict vascular conductance and blood flow in male but not female adults – attributed to effects of sympathetic activity on the peripheral vasculature. Although not a primary focus, a previous post hoc analysis of a mixed-sex cohort conducted by this group (Wan et al., 2020) found that the leg blood flow response to combined activation of the exercise pressor and chemoreflexes did not differ between male and female participants. However, as note","PeriodicalId":501632,"journal":{"name":"The Journal of Physiology","volume":" ","pages":"3639-3640"},"PeriodicalIF":5.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40516471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}