Inflammation and fibrosis play important roles in diabetic kidney disease (DKD). Previous studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists had renal protective effects. However, the mechanisms are not clear. The present study explored the effect of liraglutide (LR), a GLP-1R agonist, on the downregulation of glomerular inflammation and fibrosis in DKD by regulating the Toll-like receptor (TLR)4/myeloid differentiation marker 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in mesangial cells (MCs). In vitro, rat MCs were cultured in high glucose (HG). We found that liraglutide treatment significantly reduced the HG-mediated activation of the TLR4/MYD88/NF-κB signaling pathway, extracellular matrix (ECM)-related proteins, and inflammatory factors. A combination of TLR4 inhibitor (TAK242) and liraglutide did not synergistically inhibit inflammatory factors and ECM proteins. Furthermore, in the presence of TLR4 siRNA, liraglutide significantly blunted HG-induced expression of fibronectin protein and inflammatory factors. Importantly, TLR4 selective agonist LPS or TLR4 overexpression eliminated the improvement effects of liraglutide on the HG-induced response. In vivo, administration of liraglutide for 8 wk significantly improved the glomerular damage in streptozotocin-induced diabetic mice and reduced the expression of TLR4/MYD88/NF-κB signaling proteins, ECM protein, and inflammatory factors in renal cortex. TLR4-/- diabetic mice showed significant amelioration in urine protein excretion rate, glomerular pathological damage, inflammation, and fibrosis. Liraglutide attenuated glomerular hypertrophy, renal fibrosis, and inflammatory response in TLR4-/- diabetic mice. Taken together, our findings suggest that TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory response and ECM protein proliferation in DKD. Liraglutide alleviates inflammation and fibrosis by downregulating the TLR4/MYD88/NF-κB signaling pathway in MCs.NEW & NOTEWORTHY Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has renoprotective effect in diabetic kidney disease (DKD). In DKD, TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory responses and extracellular matrix (ECM) protein proliferation. Liraglutide attenuates renal inflammation and overexpression of ECM proteins by inhibiting TLR4/MYD88/NF-κB signaling pathway. Therefore, we have identified a new mechanism that contributes to the renal protection of GLP-1RA, thus helping to design innovative treatment strategies for diabetic patients with various complications.
{"title":"Liraglutide ameliorates inflammation and fibrosis by downregulating the TLR4/MyD88/NF-κB pathway in diabetic kidney disease.","authors":"Linjing Huang, Tingting Lin, Meizhen Shi, Peiwen Wu","doi":"10.1152/ajpregu.00083.2024","DOIUrl":"10.1152/ajpregu.00083.2024","url":null,"abstract":"<p><p>Inflammation and fibrosis play important roles in diabetic kidney disease (DKD). Previous studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists had renal protective effects. However, the mechanisms are not clear. The present study explored the effect of liraglutide (LR), a GLP-1R agonist, on the downregulation of glomerular inflammation and fibrosis in DKD by regulating the Toll-like receptor (TLR)4/myeloid differentiation marker 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in mesangial cells (MCs). In vitro, rat MCs were cultured in high glucose (HG). We found that liraglutide treatment significantly reduced the HG-mediated activation of the TLR4/MYD88/NF-κB signaling pathway, extracellular matrix (ECM)-related proteins, and inflammatory factors. A combination of TLR4 inhibitor (TAK242) and liraglutide did not synergistically inhibit inflammatory factors and ECM proteins. Furthermore, in the presence of TLR4 siRNA, liraglutide significantly blunted HG-induced expression of fibronectin protein and inflammatory factors. Importantly, TLR4 selective agonist LPS or TLR4 overexpression eliminated the improvement effects of liraglutide on the HG-induced response. In vivo, administration of liraglutide for 8 wk significantly improved the glomerular damage in streptozotocin-induced diabetic mice and reduced the expression of TLR4/MYD88/NF-κB signaling proteins, ECM protein, and inflammatory factors in renal cortex. TLR4<sup>-/-</sup> diabetic mice showed significant amelioration in urine protein excretion rate, glomerular pathological damage, inflammation, and fibrosis. Liraglutide attenuated glomerular hypertrophy, renal fibrosis, and inflammatory response in TLR4<sup>-/-</sup> diabetic mice. Taken together, our findings suggest that TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory response and ECM protein proliferation in DKD. Liraglutide alleviates inflammation and fibrosis by downregulating the TLR4/MYD88/NF-κB signaling pathway in MCs.<b>NEW & NOTEWORTHY</b> Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has renoprotective effect in diabetic kidney disease (DKD). In DKD, TLR4/MYD88/NF-κB signaling is involved in the regulation of inflammatory responses and extracellular matrix (ECM) protein proliferation. Liraglutide attenuates renal inflammation and overexpression of ECM proteins by inhibiting TLR4/MYD88/NF-κB signaling pathway. Therefore, we have identified a new mechanism that contributes to the renal protection of GLP-1RA, thus helping to design innovative treatment strategies for diabetic patients with various complications.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-05DOI: 10.1152/ajpregu.00069.2024
Fabio Zambolin, Fabio Giuseppe Laginestra, Thomas Favaretto, Gaia Giuriato, Matteo Maria Ottaviani, Federico Schena, Pablo Duro-Ocana, Jamie Stewart McPhee, Massimo Venturelli
Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.
引言:越来越多的证据表明,肌肉神经传入的激活可能会抑制中枢运动驱动力,从而影响远距离运动肌肉的收缩性能。虽然代谢感受器的这些影响已得到充分证实,但对机械和机械痛觉传入激活对运动表现疲劳性的影响却知之甚少。因此,本研究旨在探讨机械感受器和痛觉感受器对运动表现疲劳性的影响:方法:八名健康的年轻男性分别进行了四次随机实验,在实验过程中,实验者的膝关节伸肌分别处于以下状态:a)静止(CTRL);b)被动拉伸(ST);c)静止并伴有 DOMS(DOMS);或 d)被动拉伸并伴有 DOMS(DOMS+ST),同时对侧腿进行等长任务失败时间(TTF)训练。此外,还评估了最大自主收缩力(ΔMVC)、增效抽搐力(ΔQtw,pot)和自主肌肉激活力(ΔVA)的变化:结果:与 CTRL 相比,DOMS+ST(-43%)和 ST(-29%)的 TTF 均有所下降。与 CTRL(分别为 -28% vs -45%)相比,DOMS+ST 的 VA(分别为 -25% vs -8%)和 MVC 下降幅度也更大。与所有条件相比,DOMS+ST 在 TTF 的初始阶段(20%-40%-60%)RPE 明显增加:这些研究结果表明,激活 DOMS 肌肉的机械敏感和机械痛觉传入可降低对侧同源运动肢体的 TTF,部分原因是 VA 减少,从而加速了中枢疲劳机制。
{"title":"Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles.","authors":"Fabio Zambolin, Fabio Giuseppe Laginestra, Thomas Favaretto, Gaia Giuriato, Matteo Maria Ottaviani, Federico Schena, Pablo Duro-Ocana, Jamie Stewart McPhee, Massimo Venturelli","doi":"10.1152/ajpregu.00069.2024","DOIUrl":"10.1152/ajpregu.00069.2024","url":null,"abstract":"<p><p>Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: <i>1</i>) resting (CTRL), <i>2</i>) passively stretched (ST), <i>3</i>) resting with delayed onset muscle soreness (DOMS), or <i>4</i>) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQ<sub>tw,pot</sub>), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.<b>NEW & NOTEWORTHY</b> We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-22DOI: 10.1152/ajpregu.00017.2024
Ninitha Asirvatham-Jeyaraj, Miguel Anselmo, Daniel P Chantigian, Mia Larson, Emma J Lee, Manda L Keller-Ross
Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: n = 8; age: 25 ± 4 yr) and those taking OCs (OC: n = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (days 1-4) and once during the late follicular phase (days 10-14) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (P > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (P > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.NEW & NOTEWORTHY Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.
{"title":"Influence of endogenous and exogenous hormones on the cardiovascular response to lower extremity exercise and group III/IV activation in young females.","authors":"Ninitha Asirvatham-Jeyaraj, Miguel Anselmo, Daniel P Chantigian, Mia Larson, Emma J Lee, Manda L Keller-Ross","doi":"10.1152/ajpregu.00017.2024","DOIUrl":"10.1152/ajpregu.00017.2024","url":null,"abstract":"<p><p>Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: <i>n</i> = 8; age: 25 ± 4 yr) and those taking OCs (OC: <i>n</i> = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (<i>days 1-4</i>) and once during the late follicular phase (<i>days 10-14</i>) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (<i>P</i> > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (<i>P</i> > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.<b>NEW & NOTEWORTHY</b> Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptor activity, mitigate hyperthermia-induced hyperventilation. We also assessed the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (V̇E) during the heating were similar in the two trials. Moreover, when V̇E is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (38.0 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.469) and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-V̇E relation (13.5 ± 14.2 vs. 15.8 ± 15.5 L/min/°C, P = 0.831). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.NEW & NOTEWORTHY Hyperthermia leads to hyperventilation and associated cerebral hypoperfusion, both of which may impair heat tolerance. This hyperthermia-induced hyperventilation may be mediated by peripheral chemoreceptors, which can be activated by reductions in arterial pH. However, our results suggest that sodium bicarbonate ingestion, which can increase arterial pH, is not an effective intervention in alleviating hyperthermia-induced hyperventilation and cerebral hypoperfusion in resting heated humans.
高热会刺激人体通气。这种由高热引起的过度换气可能是通过激活外周化学感受器介导的,这些化学感受器与呼吸调节有关,可对各种化学刺激(包括动脉 pH 值的降低)做出反应。在此,我们研究了这样一个假设:在静止状态下被动加热时,摄入碳酸氢钠可使动脉 pH 值升高,从而减弱外周化学感受器的活动,缓解热疗引起的换气过度。我们还评估了摄入碳酸氢钠对脑血流反应的影响,脑血流反应与高热引起的换气过度有关。12 名健康男性摄入了碳酸氢钠(0.3 克/千克体重)或氯化钠(0.208 克/千克)。摄入 100 分钟后,参与者被动接受热水浸泡(42°C)和水浸服加热。在两次试验中,加热过程中食管温度(核心温度指数)和分钟通气量(VE)的增加情况相似。此外,当 VE 表示为食管温度的函数时,过度通气的核心温度阈值(37.9 ± 0.3 vs. 38.0 ± 0.4°C,P = 0.338)和核心温度-VE 关系斜率评估的高热诱导过度通气的敏感性(13.7 ± 14.9 vs. 15.8 ± 15.6 L/min/°C,P = 0.748)在两次试验之间没有差异。此外,在这两项试验中,大脑中动脉平均血流速度(脑血流指数)随着加热时间的延长而降低。这些结果表明,摄入碳酸氢钠并不能缓解高热引起的过度通气以及静息加热人体脑血流指数的降低。
{"title":"Effects of sodium bicarbonate ingestion on ventilatory and cerebrovascular responses in resting heated humans.","authors":"Akira Katagiri, Naoto Fujii, Kohei Dobashi, Yin-Feng Lai, Bun Tsuji, Takeshi Nishiyasu","doi":"10.1152/ajpregu.00161.2024","DOIUrl":"10.1152/ajpregu.00161.2024","url":null,"abstract":"<p><p>Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptor activity, mitigate hyperthermia-induced hyperventilation. We also assessed the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (V̇<sub>E</sub>) during the heating were similar in the two trials. Moreover, when V̇<sub>E</sub> is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (38.0 ± 0.3 vs. 38.0 ± 0.4°C, <i>P</i> = 0.469) and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-V̇<sub>E</sub> relation (13.5 ± 14.2 vs. 15.8 ± 15.5 L/min/°C, <i>P</i> = 0.831). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.<b>NEW & NOTEWORTHY</b> Hyperthermia leads to hyperventilation and associated cerebral hypoperfusion, both of which may impair heat tolerance. This hyperthermia-induced hyperventilation may be mediated by peripheral chemoreceptors, which can be activated by reductions in arterial pH. However, our results suggest that sodium bicarbonate ingestion, which can increase arterial pH, is not an effective intervention in alleviating hyperthermia-induced hyperventilation and cerebral hypoperfusion in resting heated humans.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1152/ajpregu.00188.2024
Jason P. Breves, Mariana A. Posada, Yixuan T. Tao, Ciaran A. Shaughnessy
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
{"title":"Salinity and prolactin regulate anoctamin 1 in the model teleost, Fundulus heteroclitus","authors":"Jason P. Breves, Mariana A. Posada, Yixuan T. Tao, Ciaran A. Shaughnessy","doi":"10.1152/ajpregu.00188.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00188.2024","url":null,"abstract":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print. <br/>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1152/ajpregu.00152.2024
Jordan B. Lee, Philip J. Millar
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
{"title":"Consideration of absolute intensity when examining sex differences in blood pressure responses during static exercise","authors":"Jordan B. Lee, Philip J. Millar","doi":"10.1152/ajpregu.00152.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00152.2024","url":null,"abstract":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print. <br/>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1152/ajpregu.00150.2024
Stephen J. Carter, Tyler H. Blechschmid, Marissa N. Baranauskas, Emily B. Long, Allison H. Gruber, John S. Raglin, Kenneth Lim, Andrew R. Coggan
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
{"title":"Pre-workout Dietary Nitrate Magnifies Training-induced Benefits to Physical Function in Late Postmenopausal Women: A Randomized Pilot Study","authors":"Stephen J. Carter, Tyler H. Blechschmid, Marissa N. Baranauskas, Emily B. Long, Allison H. Gruber, John S. Raglin, Kenneth Lim, Andrew R. Coggan","doi":"10.1152/ajpregu.00150.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00150.2024","url":null,"abstract":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print. <br/>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1152/ajpregu.00128.2024
Julio D. Zuarth Gonzalez, Marco Mottinelli, Christopher R. McCurdy, Guillaume de Lartigue, Lance R. McMahon, Jenny L. Wilkerson
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print.
美国生理学杂志-调节、综合和比较生理学》,提前出版。
{"title":"Mitragynine and Morphine Produce Dose-dependent Bimodal Action on Food but not Water Intake in Rats","authors":"Julio D. Zuarth Gonzalez, Marco Mottinelli, Christopher R. McCurdy, Guillaume de Lartigue, Lance R. McMahon, Jenny L. Wilkerson","doi":"10.1152/ajpregu.00128.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00128.2024","url":null,"abstract":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Ahead of Print. <br/>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1152/ajpregu.00164.2024
Benjamin J Ryan, David E Barney, Julie L McNiff, Devin J Drummer, Emily E Howard, Jess A Gwin, Christopher T Carrigan, Nancy E Murphy, Marques A Wilson, Stefan M Pasiakos, James P McClung, Lee M Margolis
Strenuous physical training increases total blood volume (BV) through expansion of plasma (PV) and red cell volumes (RCV). In contrast, exogenous erythropoietin (EPO) treatment increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO treatment on BV and markers of systemic and muscle iron homeostasis. In this longitudinal study, 8 healthy non-anemic males were treated with EPO (50 IU/kg body mass, 3x/week, subcutaneously) across 28 days of strenuous training (4d/week, exercise energy expenditures of 1334±24 kcal/d) while consuming a controlled, energy-balanced diet providing 39±4 mg/d iron. Before (PRE) and after (POST) intervention, BV compartments were measured using carbon monoxide rebreathing, and markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Training + EPO increased (p<0.01) RCV (13±6%) and BV (5±4%), whereas PV remained unchanged (p=0.86). The expansion of RCV was accompanied by a large decrease in whole-body iron stores, as indicated by decreased (p<0.01) ferritin (-77±10%) and hepcidin (-49±23%) concentrations in plasma. Training + EPO decreased (p<0.01) muscle protein abundance of ferritin (-25±20%) and increased (p<0.05) transferrin receptor (47±56%). These novel findings illustrate that strenuous training combined with EPO results in both increased total oxygen carrying capacity and hypervolemia in young healthy males. The decrease in plasma and muscle ferritin suggests that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole-body and skeletal muscle iron stores.
{"title":"Strenuous training combined with erythropoietin induces red cell volume expansion-mediated hypervolemia and alters systemic and skeletal muscle iron homeostasis.","authors":"Benjamin J Ryan, David E Barney, Julie L McNiff, Devin J Drummer, Emily E Howard, Jess A Gwin, Christopher T Carrigan, Nancy E Murphy, Marques A Wilson, Stefan M Pasiakos, James P McClung, Lee M Margolis","doi":"10.1152/ajpregu.00164.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00164.2024","url":null,"abstract":"<p><p>Strenuous physical training increases total blood volume (BV) through expansion of plasma (PV) and red cell volumes (RCV). In contrast, exogenous erythropoietin (EPO) treatment increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO treatment on BV and markers of systemic and muscle iron homeostasis. In this longitudinal study, 8 healthy non-anemic males were treated with EPO (50 IU/kg body mass, 3x/week, subcutaneously) across 28 days of strenuous training (4d/week, exercise energy expenditures of 1334±24 kcal/d) while consuming a controlled, energy-balanced diet providing 39±4 mg/d iron. Before (PRE) and after (POST) intervention, BV compartments were measured using carbon monoxide rebreathing, and markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Training + EPO increased (p<0.01) RCV (13±6%) and BV (5±4%), whereas PV remained unchanged (p=0.86). The expansion of RCV was accompanied by a large decrease in whole-body iron stores, as indicated by decreased (p<0.01) ferritin (-77±10%) and hepcidin (-49±23%) concentrations in plasma. Training + EPO decreased (p<0.01) muscle protein abundance of ferritin (-25±20%) and increased (p<0.05) transferrin receptor (47±56%). These novel findings illustrate that strenuous training combined with EPO results in both increased total oxygen carrying capacity and hypervolemia in young healthy males. The decrease in plasma and muscle ferritin suggests that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole-body and skeletal muscle iron stores.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1152/ajpregu.00085.2024
Eva-Maria S Bønnelycke, Tommaso A Giacon, Gerardo Bosco, Jana M Kainerstorfer, Matteo Paganini, Alexander Ruesch, Jingyi Wu, J Chris McKnight
While existing literature covers significant detail on the physiology of human freediving, the lack of standardized protocols has hindered comparisons due to confounding variables such as exercise and depth. By accounting for these variables, direct depth-dependent impacts on cardiovascular and blood oxygen regulation can be investigated. In this study, depth-dependent effects on 1) cerebral hemodynamic and oxygenation changes, 2) arterial oxygen saturation (SpO2), and 3) heart rate during breath-hold diving without confounding effects of exercise were investigated. Six freedivers (51.0 ± 12.6 years; mean ± s.d.), instrumented with continuous-wave near-infrared spectroscopy for monitoring cerebral hemodynamic and oxygenation measurements, heart rate and SpO2, performed sled-assisted breath-hold dives to 15 m and 42 m. Arterial blood gas tensions were validated through cross-sectional periodic blood sampling. Cerebral hemodynamic changes were characteristic of breath-hold diving, with changes during ascent from both depths likely driven by decreasing SpO2 due to lung expansion. While SpO2 was significantly lower following 42 m dives (t(5) = -4.183, p < 0.05), mean cerebral arterial-venous blood oxygen saturation remained at 74% following dives to both depths. Cerebral oxygenation during ascent from 42 m may have been maintained through increased arterial delivery. Heart rate was variable with no significant difference in minimum heart rate between both depths (t(5) = -1.017, p > 0.05). This study presents a standardized methodology, which could provide a basis for future research on human freediving physiology and uncover ways in which freedivers can reduce potential risks of the sport.
{"title":"Cerebral hemodynamic and systemic physiological changes in trained freedivers completing sled-assisted dives to two different depths.","authors":"Eva-Maria S Bønnelycke, Tommaso A Giacon, Gerardo Bosco, Jana M Kainerstorfer, Matteo Paganini, Alexander Ruesch, Jingyi Wu, J Chris McKnight","doi":"10.1152/ajpregu.00085.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00085.2024","url":null,"abstract":"<p><p>While existing literature covers significant detail on the physiology of human freediving, the lack of standardized protocols has hindered comparisons due to confounding variables such as exercise and depth. By accounting for these variables, direct depth-dependent impacts on cardiovascular and blood oxygen regulation can be investigated. In this study, depth-dependent effects on 1) cerebral hemodynamic and oxygenation changes, 2) arterial oxygen saturation (SpO<sub>2</sub>), and 3) heart rate during breath-hold diving without confounding effects of exercise were investigated. Six freedivers (51.0 ± 12.6 years; mean ± s.d.), instrumented with continuous-wave near-infrared spectroscopy for monitoring cerebral hemodynamic and oxygenation measurements, heart rate and SpO<sub>2</sub>, performed sled-assisted breath-hold dives to 15 m and 42 m. Arterial blood gas tensions were validated through cross-sectional periodic blood sampling. Cerebral hemodynamic changes were characteristic of breath-hold diving, with changes during ascent from both depths likely driven by decreasing SpO<sub>2</sub> due to lung expansion. While SpO<sub>2</sub> was significantly lower following 42 m dives (t(5) = -4.183, <i>p <</i> 0.05), mean cerebral arterial-venous blood oxygen saturation remained at 74% following dives to both depths. Cerebral oxygenation during ascent from 42 m may have been maintained through increased arterial delivery. Heart rate was variable with no significant difference in minimum heart rate between both depths (t(5) = -1.017, <i>p ></i> 0.05). This study presents a standardized methodology, which could provide a basis for future research on human freediving physiology and uncover ways in which freedivers can reduce potential risks of the sport.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}