American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Post-exercise hot-water immersion is not effective for ribosome biogenesis in rat skeletal muscle.","authors":"Takaya Kotani, Yuki Tamura, Karina Kouzaki, Kazushige Sasaki, Koichi Nakazato","doi":"10.1152/ajpregu.00068.2024","DOIUrl":"10.1152/ajpregu.00068.2024","url":null,"abstract":"<p><p>Ribosome biogenesis is an important regulator of skeletal muscle hypertrophy induced by repeated bouts of resistance exercise (RE). Hot-water immersion (HWI), a widely used post-exercise recovery strategy, activates the mechanistic target of rapamycin (mTOR) signaling, a key regulator of ribosome biogenesis in skeletal muscle. However, the effect of HWI on skeletal muscle ribosome biogenesis is not well understood. Here, we aimed to investigate the effects of HWI and post-exercise HWI on ribosome biogenesis using a rat RE model. Male Sprague-Dawley rats were randomly assigned to HWI and non-HWI groups. In both groups, the right leg was isometrically exercised using transcutaneous electrical stimulation, while the left leg was used as an internal non-RE control. Following RE, both limbs were immersed in hot water (41.2 ± 0.03°C) for 20 min under isoflurane anesthesia in the HWI group and the gastrocnemius muscles were sampled at 3- and 24-h post-exercise. HWI significantly increased mTOR signaling and <i>c-Myc</i> mRNA expression, whereas post-exercise HWI significantly increased transcription initiation factor-IA mRNA expression. However, neither HWI nor post-exercise HWI enhanced 45S pre-rRNA expression, ribosomal RNA, or ribosomal protein content. In addition, HWI tended to decrease 28S rRNA and 18S rRNA content, widely used markers of ribosome content. These results suggest that HWI as a post-exercise recovery is not effective in activating ribosome biogenesis.<b>NEW & NOTEWORTHY</b> Ribosome biogenesis is crucial in resistance exercise (RE)-induced skeletal muscle hypertrophy. This study examined the effects of hot-water immersion (HWI) on ribosome biogenesis after RE. HWI and post-exercise HWI increased c-<i>Myc</i> and transcription initiation factor-IA mRNA but did not alter ribosomal RNA transcription or ribosomal protein content. HWI tended to decrease 28S and 18S ribosomal RNA. These findings suggest that HWI, as a recovery strategy, does not effectively promote ribosome biogenesis or muscle protein synthesis.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R601-R615"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567598","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}

{"title":"Steering toward new horizons: a vision for the future of the <i>American Journal of Physiology-Regulatory, Integrative and Comparative Physiology</i>.","authors":"Kamal Rahmouni","doi":"10.1152/ajpregu.00252.2024","DOIUrl":"10.1152/ajpregu.00252.2024","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R525-R527"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is muscle sympathetic nerve activity associated with cerebral blood velocity? A partial coherence analysis.","authors":"Edgar Toschi-Dias, Ricardo C Nogueira, Edna O Silva, Graziela Amaro-Vicente, Carlos E Negrão, Maria Urbana P B Rondon, Ronney B Panerai","doi":"10.1152/ajpregu.00112.2024","DOIUrl":"10.1152/ajpregu.00112.2024","url":null,"abstract":"<p><p>Despite some evidence, the role of sympathetic nerve activity in the regulation of cerebral blood flow remains controversial. In humans, muscle sympathetic nervous activity (MSNA) is the only direct measure of sympathetic nerve activity that can be recorded with sufficient temporal resolution to allow association with dynamic regulation of cerebral blood velocity (CBv). This study tested the hypothesis that MSNA is associated with the regulation of CBv at rest and during different physiological maneuvers. Nine healthy subjects underwent two sympathoexcitatory maneuvers: <i>1</i>) isometric handgrip exercise (HGR), and <i>2</i>) cold pressor test (CPT). Mean arterial pressure (MAP; oscillometric method), CBv (transcranial Doppler ultrasound), and MSNA (microneurography) were measured continuously during experimental protocols. Ordinary and partial coherences of the MAP, CBv, and MSNA time series were estimated by transfer function analysis in the low-frequency range (0.07-0.20 Hz), using MAP and MSNA as inputs and CBv as the output variable. When the influence of MSNA was taken into account, the partial coherences between MAP and CBv were considerably reduced at baseline (<i>P</i> < 0.01), HGR (<i>P</i> = 0.02), and CPT (<i>P</i> < 0.01). Similarly, when the influence of MAP was taken into account, the coherence between MSNA and CBv was considerably reduced at baseline (<i>P</i> < 0.01), HGR (<i>P</i> = 0.02), and CPT (<i>P</i> = 0.01), leading to the conclusion, that MSNA was associated to dynamic regulation of CBv. Partial coherence analysis is a promising method for assessing the influence of the sympathetic nervous system on cerebral hemodynamics.<b>NEW & NOTEWORTHY</b> Partial coherence analysis has been instrumental in demonstrating, for the first time, that cerebral blood velocity (CBv) is continuously influenced, not only by fluctuations in mean arterial pressure but also muscle sympathetic nervous activity (MSNA), leading to similar dynamic responses at rest and during different sympathoexcitatory maneuvers in healthy subjects. Modeling the temporal relationship between MSNA and CBv opens new opportunities for advancing knowledge regarding the role of the sympathetic nervous system in the regulation of cerebral circulation in health and disease.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R590-R600"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492996","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}

{"title":"Acute salivary antimicrobial peptide secretion response to different exercise intensities and durations.","authors":"Reita Ito, Takamasa Uchino, Masataka Uchida, Shumpei Fujie, Keiko Iemitsu, Chihiro Kojima, Mariko Nakamura, Kazuhiro Shimizu, Yuko Tanimura, Yasushi Shinohara, Takeshi Hashimoto, Tadao Isaka, Motoyuki Iemitsu","doi":"10.1152/ajpregu.00132.2024","DOIUrl":"10.1152/ajpregu.00132.2024","url":null,"abstract":"<p><p>Antimicrobial peptides, key players of innate mucosal immunity in the oral cavity, exert antibacterial and bacteriolytic effects. This study aimed to clarify the effects of acute exercise at different intensities and durations on salivary antimicrobial peptide levels. In a randomized crossover trial, 14 young healthy untrained men performed intensity trials [cycling at 35%, 55%, and 75% of maximal oxygen uptake (V̇o_2max) for 30 min] and duration trials (cycling at 55% V̇o_2max for 30, 60, and 90 min). Saliva samples were collected at baseline and 0 and 60 min after exercise. In intensity trials, the change in salivary lactoferrin levels from baseline to 0 min after 30 min exercise was greater at 75% V̇o_2max exercise intensity compared with that at 35% V̇o_2max. Furthermore, the change in salivary human β-defensin-2 (HBD-2) levels was greater at 75% V̇o_2max compared with that at 35% and 55% V̇o_2max. Salivary lysozyme levels increased after exercise, independent of exercise intensity. However, salivary LL-37 levels did not change after exercise at any intensity. In addition, in duration trials, the change in salivary levels of LL-37 and HBD-2 from baseline to 0 min after exercise at 55% V̇o_2max was greater after 60 and 90 min of exercise compared with that after 30 min of exercise. However, salivary lactoferrin and lysozyme levels increased after exercise, independent of exercise duration. Our findings suggest that secretory responses to acute exercise with exercise intensity and duration differ among salivary antimicrobial peptides.<b>NEW & NOTEWORTHY</b> We investigated the effects of acute exercise at different intensities and durations on the immune response to salivary antimicrobial peptides in young healthy men. Levels of four salivary antimicrobial peptides increased after exercise dependently or independently of exercise intensity and duration, whereas some salivary antimicrobial peptides did not change after exercise. These findings suggest that the secretory responses to acute exercise with different intensities and durations differ among salivary antimicrobial peptides.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R616-R622"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999282","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}

{"title":"Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults.","authors":"Gregory W McGarr, Caroline Li-Maloney, Kelli E King, Kristina-Marie T Janetos, Naoto Fujii, Tatsuro Amano, Glen P Kenny","doi":"10.1152/ajpregu.00127.2024","DOIUrl":"10.1152/ajpregu.00127.2024","url":null,"abstract":"<p><p>We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVC_max) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with <i>1</i>) Ringer solution (control), <i>2</i>) 100 µM apocynin (NADPH oxidase inhibitor), <i>3</i>) 10 µM allopurinol (xanthine oxidase inhibitor), or <i>4</i>) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (<i>protocol 1</i>) and whole body heating (<i>protocol 2</i>). In <i>protocol 1</i>, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In <i>protocol 2</i>, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In <i>protocol 1</i>, there were significant treatment site by age interactions for the 39°C (<i>P</i> = 0.015) and 42°C (<i>P</i> = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In <i>protocol</i> 2, there was a significant treatment site by age interaction (<i>P</i> < 0.001), where %CVC_max in older adults was 11.0% [7.4, 14.6] higher for apocynin (<i>P</i> < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (<i>P</i> < 0.001), and 4.8% [1.3, 8.4] higher for tempol (<i>P</i> = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.<b>NEW & NOTEWORTHY</b> We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R543-R552"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143012","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}

{"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":"10.1152/ajpregu.00164.2024","url":null,"abstract":"<p><p>Strenuous physical training increases total blood volume (BV) through expansion of plasma volume (PV) and red cell volume (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, eight healthy nonanemic males were treated with EPO (50 IU/kg body mass, three times per week, sc) across 28 days of strenuous training (4 days/wk, exercise energy expenditures of 1,334 ± 24 kcal/day) while consuming a controlled, energy-balanced diet providing 39 ± 4 mg/day 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 (<i>P</i> < 0.01) RCV (13 ± 6%) and BV (5 ± 4%), whereas PV remained unchanged (<i>P</i> = 0.86). The expansion of RCV was accompanied by a large decrease in whole body iron stores, as indicated by decreased (<i>P</i> < 0.01) ferritin (-77 ± 10%) and hepcidin (-49 ± 23%) concentrations in plasma. Training + EPO decreased (<i>P</i> < 0.01) muscle protein abundance of ferritin (-25 ± 20%) and increased (<i>P</i> < 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.<b>NEW & NOTEWORTHY</b> Strenuous exercise training combined with erythropoietin (EPO) treatment increases blood volume, driven exclusively by red cell volume expansion. This hematological adaptation results in increased total oxygen-carrying capacity and hypervolemia. The marked upregulation of erythropoiesis with training + EPO reduces whole body iron stores and circulating hepcidin concentrations. The finding that the abundance of ferritin in muscle decreased after training + EPO suggests that muscle may release iron to support red blood cell production.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R473-R478"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563636/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during a cold pressor test.","authors":"Caitlin P Jarrard, Zachary J McKenna, Whitley C Atkins, Josh Foster, Joseph M Hendrix, Noah P Jouett, Zachary R Oldham, Benjamin J LeBlanc, Joseph C Watso, Craig G Crandall","doi":"10.1152/ajpregu.00003.2024","DOIUrl":"10.1152/ajpregu.00003.2024","url":null,"abstract":"<p><p>Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: <i>1</i>) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and <i>2</i>) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (<i>aim 1</i>). After a recovery period, participants completed a cold pressor test (CPT; <i>aim 2</i>). Addressing the first aim, tolerance to LBNP was not different between trials (<i>P</i> = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time <i>P</i> < 0.001, trial <i>P</i> = 0.477, interaction <i>P</i> = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time <i>P</i> < 0.001, trial <i>P</i> = 0.626, interaction <i>P</i> = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (<i>P</i> < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (<i>P</i> = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.<b>NEW & NOTEWORTHY</b> Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R497-R507"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension restricts leg blood flow and aggravates neuromuscular fatigue during human locomotion in males.","authors":"Taylor S Thurston, Joshua C Weavil, Hsuan-Yu Wan, Mark A Supiano, Philip A Kithas, Markus Amann","doi":"10.1152/ajpregu.00117.2024","DOIUrl":"10.1152/ajpregu.00117.2024","url":null,"abstract":"<p><p>Patients with hypertension (HTN) are characterized by exaggerated vascular resistance and mean arterial pressure (MAP) and a compromised leg blood flow (Q_L) response to exercise recruiting a small muscle mass. However, the impact of hypertension on peripheral hemodynamics and the development of neuromuscular fatigue during locomotor activities, which critically depends on Q_L, remain unknown. Eight HTN (143 ± 11 mmHg/95 ± 6 mmHg; 45 ± 13 yr) and eight matched (age and activity) controls (120 ± 6 mmHg/77 ± 7 mmHg; CTRL) performed constant-load cycling exercise at 25, 50, and 75 W (for 4 min each) and at 165 ± 41 W (for 5 min). Exercise-induced locomotor muscle fatigue was quantified as the pre- to postexercise change in quadriceps twitch-torque (Δ<i>Q</i>_tw, peripheral fatigue) and voluntary activation (ΔVA%, central fatigue). Q_L (Doppler ultrasound) and leg vascular conductance (LVC) were determined during cycling at 25, 50, and 75 W. Heart rate and ventilatory responses were recorded during all intensities. MAP during exercise was, on average, ∼21 mmHg higher (<i>P</i> = 0.002) and LVC ∼39% lower (<i>P</i> = 0.001) in HTN compared with CTRL. Q_L was consistently between 20 and 30% lower (<i>P</i> = 0.004), and heart rate was significantly higher in HTN. Exercise-induced peripheral (Δ<i>Q</i>_tw: -53 ± 19% vs. -25 ± 23%) and central (ΔVA%: -7 ± 5% vs. -3 ± 2%) fatigue was significantly greater in HTN compared with CTRL. In addition to an exaggerated MAP, LVC and Q_L were lower during exercise in HTN compared with CTRL. Given the critical role of Q_L in determining the development of neuromuscular fatigue, these hemodynamic impairments likely accounted for the faster development of neuromuscular fatigue characterizing hypertensive individuals during locomotor exercise. <b>NEW & NOTEWORTHY</b> The impact of primary hypertension on the cardiovascular and neuromuscular fatigue response to locomotor exercise is unknown. We compared central and peripheral hemodynamics and the development of central and peripheral fatigue during cycling exercise in patients with stage I/II hypertension and age- and activity-matched healthy individuals. In addition to a significantly elevated blood pressure, hypertensive patients were, compared with their nonhypertensive counterparts, also characterized by considerable leg blood flow limitations and impaired neuromuscular fatigue resistance.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R517-R524"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous and evoked angiotensin II sniffer cell activity in the lamina terminalis in vitro.","authors":"George E Farmer, J Thomas Cunningham","doi":"10.1152/ajpregu.00227.2023","DOIUrl":"10.1152/ajpregu.00227.2023","url":null,"abstract":"<p><p>Angiotensin II (ANG II) has been shown to have central nervous system effects. Although tissue renin-angiotensin systems (RAS) have been demonstrated in multiple tissues, the existence of a brain RAS is still a matter of debate. These studies test for angiotensin release from brain slices prepared from adult male Sprague-Dawley rats and male and female renin knock-out rats using Chinese hamster ovary cells modified to express both the angiotensin II type 1 receptor and a fluorescent calcium indicator. Sniffer cells were placed on the slices and calcium transients were measured from those located on or adjacent to the median preoptic nucleus with and without stimulation of the subfornical organ. Bath application of tetrodotoxin (1 µM) significantly attenuated spontaneous events while abolishing evoked sniffer cell activity. Bath application of dl-AP4 (10 µM, glutamatergic antagonist) did not affect either spontaneous or evoked release. Incubating the slices with fluorocitrate to inactive astrocytes did not influence sniffer cell activity in the MnPO. Pharmacological experiments indicate that ANG II release is largely both renin (aliskiren 10 µM) and ACE-1 (captopril 100 µM) dependent. However, experiments with brain slices prepared from male and female Renin knock-out rats suggest that alternative synthetic pathways may exist. Finally, these studies demonstrate that increases in ANG II release are observed following 7 days of chronic intermittent hypoxia. These studies suggest the existence of a tissue-specific RAS in the brain that involves canonical and alternative ANG II synthetic pathways and is upregulated in an animal model of sleep apnea.<b>NEW & NOTEWORTHY</b> These studies used Chinese hamster ovary cells that were cloned to express an angiotensin receptor (<i>At1ra</i>) and a calcium indicator (R-GECO) to detect the release of angiotensin from brain slices containing the lamina terminalis of rats. Some of the experiments use tissue from renin knockout rats. The results support the existence of an angiotensin system in the brain that may involve alternative synthetic pathways and is upregulated by intermittent hypoxia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R486-R496"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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^-/- 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.<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":" ","pages":"R410-R422"},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483077/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}