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

{"title":"Relationship between regional sympathetic vascular transduction and sympathetic transduction of blood pressure in young adults at rest.","authors":"Devin G McCarthy, Massimo Nardone, Kathryn Pfundt, Philip J Millar","doi":"10.1152/ajpregu.00199.2024","DOIUrl":"10.1152/ajpregu.00199.2024","url":null,"abstract":"<p><p>A burst of muscle sympathetic nerve activity (MSNA) induces vasoconstriction that transiently reduces regional vascular conductance and increases systemic blood pressure (BP) over the subsequent 4-8 cardiac cycles. These responses are termed sympathetic neurovascular transduction and sympathetic transduction of BP, respectively. Sympathetic transduction of BP is commonly calculated and interpreted as a proxy measure for regional sympathetic neurovascular transduction despite the systemic nature of BP regulation. The present analysis tested whether the peak change in signal-averaged sympathetic transduction of BP was correlated to the change in regional sympathetic vascular transduction at rest. Fourteen adults (5 females, 23 ± 3 yr) arrived at the laboratory, ate a standardized meal, and rested for 90-120 min. MSNA (fibular nerve microneurography), heart rate (electrocardiography), beat-to-beat BP (finger photoplethysmography), and superficial femoral artery blood flow (Doppler ultrasound) were obtained continuously for 10 min in the supine position. Femoral vascular conductance (FVC) was calculated as blood flow divided by mean arterial BP. The peak change in diastolic BP following a burst of MSNA was correlated to the corresponding nadir change in femoral vascular conductance (<i>r</i> = -0.58 [-0.07 to -0.85], <i>P</i> = 0.03) and superficial femoral artery blood flow (<i>r</i> = -0.54 [-0.17 to -0.83], <i>P</i> = 0.04). The nadir change in diastolic BP in cardiac cycles not following an MSNA burst was correlated to the peak change in femoral vascular conductance (<i>r</i> = -0.42 [-0.83 to 0.00], <i>P</i> = 0.05), but not superficial femoral artery blood flow (<i>r</i> = 0.41 [-0.77 to 0.15], <i>P</i> = 0.14). In conclusion, more commonly assessed sympathetic transduction of BP provides moderate insight into regional sympathetic neurovascular transduction.<b>NEW & NOTEWORTHY</b> The majority of studies have used signal-averaged sympathetic transduction of blood pressure as a generalized measure of transduction. In this analysis, we show that sympathetic transduction of blood pressure and regional sympathetic vascular transduction were moderately correlated in healthy adults at rest. The moderate strength of this relationship highlights potential differences between regional and systemic assessments of sympathetic transduction and suggests that future work should choose the transduction measure best aligned with the research question.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387293","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":"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":"10.1152/ajpregu.00085.2024","url":null,"abstract":"<p><p>Although 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 <i>1</i>) cerebral hemodynamic and oxygenation changes, <i>2</i>) arterial oxygen saturation ([Formula: see text]), and <i>3</i>) heart rate during breath-hold diving without confounding effects of exercise were investigated. Six freedivers (51.0 ± 12.6 yr; means ± SD), instrumented with continuous-wave near-infrared spectroscopy for monitoring cerebral hemodynamic and oxygenation measurements, heart rate, and [Formula: see text], 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 [Formula: see text] due to lung expansion. Although [Formula: see text] was significantly lower following 42-m dives [<i>t</i>(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 [<i>t</i>(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.<b>NEW & NOTEWORTHY</b> We present a standardized methodology in which trained breath-hold divers instrumented with wearable near-infrared spectroscopy (NIRS) technology and a cannula for arterial blood sampling completed sled-assisted dives to two different dive depths to account for the confounding factors of exercise and depth during breath-hold diving. In our investigation, we highlight the utility of wearable NIRS systems for continuous hemodynamic and oxygenation monitoring to investigate the impacts of hydrostatic pressure on cardiovascular and blood oxygen regulation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","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}

{"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":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"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":"Comparative analysis of acute eccentric contraction-induced changes to the skeletal muscle transcriptome in young and aged mice and humans.","authors":"Jake R Boykin, Jennifer L Steiner, Grant R Laskin, Michael D Roberts, Cynthia Vied, Craig Rg Willis, Timothy Etheridge, Bradley S Gordon","doi":"10.1152/ajpregu.00224.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00224.2024","url":null,"abstract":"<p><p>Adaptations to skeletal muscle following resistance exercise are due in part to changes to the skeletal muscle transcriptome. While transcriptional changes in response to resistance exercise occur in young and aged muscle, aging alters this response. Rodent models have served great utility in defining regulatory factors that underscore the influence of mechanical load and aging on changes to skeletal muscle phenotype. Unilateral eccentric contractions in young and aged rodents are widely used to model resistance exercise in humans. However, the extent to which unilateral eccentric contractions in young and aged rodents mimics the transcriptional response in humans remains unknown. We re-analyzed two publicly available RNA sequencing datasets from young and aged mice and humans that were subjected to acute eccentric contractions to define key similarities and differences to the muscle transcriptional response following this exercise modality. The effect of aging on the number of contraction-sensitive genes, the distribution patterns of those genes into unique/common categories, and the cellular pathways associated with the differentially expressed genes (DEGs) were similar in mice and humans. However, there was little overlap between species when comparing specific contraction-sensitive DEGs within the same age group. There were strong intraspecies relationships for the common transcription factors predicted to influence the contraction-sensitive gene sets, whereas interspecies relationships were weak. Overall, these data demonstrate key similarities between mice and humans for the contraction-induced changes to the muscle transcriptome, but we posit species-specific responses exist and should be taken into consideration when attempting to translate rodent eccentric exercise models.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567575","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":"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":"https://doi.org/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℃) 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 c-Myc 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. Additionally, 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.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-04","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":"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":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","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}

{"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":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}