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

{"title":"Stimulus temperature modulates the psychophysical dimensions of salt taste.","authors":"Mariela E Marques, Alan C Spector, Roberto Vincis","doi":"10.1152/ajpregu.00170.2026","DOIUrl":"10.1152/ajpregu.00170.2026","url":null,"abstract":"<p><p>Temperature is a fundamental yet understudied parameter of gustatory experience. In this study, we designed a set of experiments that examined how stimulus temperature affects the motivational and sensory-discriminative properties of sodium (NaCl) and nonsodium (KCl) salts. In brief-access tests, water-deprived mice consistently preferred cool (14°C) over warm (36°C) stimuli regardless of salt content. Progressive ratio tests confirmed that cool stimuli possess greater appetitive efficacy, suggesting that, under our experimental conditions, water deprivation may confound temperature preferences in brief-access procedures. In contrast, operant conditioning tasks revealed robust temperature effects on sensory-discriminative function. In a two-response taste detection task in which mice were trained to distinguish each salt from water, enhanced sensitivity to both NaCl and KCl was observed at 36°C compared with 14°C, with detection thresholds significantly lower at warm temperatures. Critically, in discrimination tasks where mice were required to distinguish between NaCl and KCl with stimulus intensity controlled by anchoring concentrations at their respective detection thresholds, mice showed significantly impaired discrimination performance at 36°C compared with 14°C, indicating that the qualitative signatures of the two salts became perceptually more similar at the warmer temperatures. These findings demonstrate that temperature profoundly modulates the sensory-discriminative properties of salts: although warm temperatures enhance detection sensitivity, they simultaneously reduce qualitative discriminability between sodium and nonsodium salts. Overall, these results have implications for the operational principles of taste function and highlight the promising possibility that temperature manipulation could serve as an effective strategy for dietary sodium reduction.<b>NEW & NOTEWORTHY</b> Despite being a fundamental parameter of gustatory experience, how temperature shapes taste perception remains poorly understood. Using a multifaceted behavioral approach in mice, we found that water deprivation confounds temperature-driven motivational responses. In contrast, warm temperatures both lowered detection thresholds for NaCl and KCl and impaired discrimination between the two salts, revealing that temperature modulates the perceptual similarity between sodium and nonsodium salts with implications for taste neuroscience and sodium reduction strategies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R291-R306"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468400","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":"Adipocyte aryl hydrocarbon receptors mediate sex differences in pyocyanin-induced weight loss.","authors":"Nika Larian, Charles M Ensor, Yasir AlSiraj, Lisa A Cassis","doi":"10.1152/ajpregu.00007.2026","DOIUrl":"10.1152/ajpregu.00007.2026","url":null,"abstract":"<p><p>Pyocyanin (PYO) is a <i>Pseudomonas aeruginosa</i> virulence factor metabolite that is an aryl hydrocarbon receptor (AhR) ligand. In addition to liver, adipocytes express AhR that regulates adipocyte differentiation and inflammatory adipokines. Previous studies demonstrated that PYO administration reduced body weight and adipose mass of mice. The purpose of this study was to define the role of AhR in PYO-induced regulation of 3T3-L1 adipocyte differentiation in vitro, and body weight and fat mass in vivo in male and female mice. PYO-induced reductions in adipocyte differentiation were not abolished by AhR antagonists. However, a competitive AhR antagonist reduced PYO-induced increases in adipocyte <i>CYP1a1</i> mRNA abundance. PYO-induced reductions in body weight of male and female mice were not abolished in <i>AhR^+/-</i> mice. In contrast, male mice with adipocyte AhR deficiency exhibited reductions in PYO-induced regulation of body weight, whereas female adipocyte AhR-deficient mice exhibited augmented PYO-induced body weight reductions. Adipocyte AhR deficiency reduced PYO-induced elevations of adipose tissue <i>CYP1a1</i> mRNA abundance in both sexes. PYO increased glycerol release from adipose explants of females, but not males, an effect that was abolished in explants from female adipocyte AhR-deficient mice. These results demonstrate that PYO regulates adipocyte differentiation through AhR-independent mechanisms. In males, PYO effects on body weight are partially adipocyte AhR<i>-</i>mediated. However, adipocyte AhR-deficient females exhibit potentiation of PYO regulation of body weight. These findings suggest that adipocyte AhR may differentially regulate susceptibility to <i>P. aeruginosa</i>-induced cachexia in males and females.<b>NEW & NOTEWORTHY</b> We examined effects of AhR antagonists on adipocyte differentiation and adipocyte AhR receptors in effects of pyocyanin to induce weight loss in male and female mice. In males, adipocyte AhR mediated pyocyanin-induced regulation of body weight, whereas in females, removal of adipocyte AhR potentiated pyocyanin-induced reductions of body weight. These results suggest cachexia from systemic <i>P. aeruginosa</i> infections may differ between males and females due to sex differences in pyocyanin effects at adipocyte AhR.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R186-R197"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209866","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":"\"Should I stay or should I go?\" How do our muscles respond to spaceflight stressors long after we return to Earth?","authors":"Thaysa Ghiarone, Kleiton A S Silva","doi":"10.1152/ajpregu.00225.2026","DOIUrl":"10.1152/ajpregu.00225.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R254-R256"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409963","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":"Retraction for Hu, Research progress on thirst and dry mouth after alcohol consumption.","authors":"","doi":"10.1152/ajpregu.00208.2025","DOIUrl":"10.1152/ajpregu.00208.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R52"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430276","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":"Arterial CO₂ partial pressure is a key modulator of active muscle hypoperfusion mediated by diving reflex in exercising young adults.","authors":"Ryoko Matsutake, Masashi Ichinose, Takeshi Nishiyasu, Tomomi Fujimoto, Kohei Dobashi, Naoto Fujii","doi":"10.1152/ajpregu.00032.2026","DOIUrl":"10.1152/ajpregu.00032.2026","url":null,"abstract":"<p><p>Voluntary apnea markedly attenuates exercise-induced increases in active muscle blood flow, a response known as the diving reflex, which is thought to preserve oxygen within the body. However, the underlying mechanisms of this response remain unknown. Since voluntary apnea elevates arterial CO₂ partial pressure, which can induce vasoconstriction in active muscles during exercise, we hypothesized that arterial CO₂ partial pressure modulates diving reflex-related regulation of active muscle blood flow. Fourteen young adults (1 female) performed maximal-duration breath-holding during a dynamic two-legged knee extension exercise that elicits a heart rate of 100 beats·min^-1. The apnea was preceded by 3-min voluntary hyperventilation, which reduced end-tidal CO₂ partial pressure to ∼20 mmHg (i.e., hypocapnic hyperventilation). As a control trial, hyperventilation was performed while keeping the end-tidal CO₂ partial pressure at normocapnic level by CO₂ inhalation (normocapnic hyperventilation). Hypocapnic hyperventilation increased apnea duration compared with normocapnic hyperventilation (52 ± 16 vs. 31 ± 13 s, <i>P</i> < 0.001). At matched time points between conditions, leg blood flow was higher in the hypocapnic than in the normocapnic hyperventilation condition (2236 ± 583 vs. 1643 ± 576 mL·min^-1, <i>P</i> = 0.002). Hypocapnic hyperventilation also attenuated apnea-induced bradycardia, as well as increases in mean arterial pressure and middle cerebral artery mean blood velocity, compared with normocapnic hyperventilation at the iso-time point (all <i>P</i> < 0.001). We show that, based on end-tidal CO₂ measurements, arterial CO₂ partial pressure appears to modulate diving reflex-related active muscle hypoperfusion, as well as bradycardia, pressor response, and cerebral hyperemia in exercising adults.<b>NEW & NOTEWORTHY</b> We show that arterial CO₂ partial pressure is a major factor that largely influences apnea-induced vasoconstriction in exercising muscles as well as bradycardia, pressor responses, and cerebral hyperemia during exercise. Thus, the diving reflex, which is traditionally regarded as an oxygen-conservation response, may also serve to regulate CO₂ homeostasis.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R23-R32"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986113","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":"Unilateral lower limb suspension affects motor unit action potential train characteristics in a size-dependent manner during high force isometric knee extension.","authors":"Jordan Hughes, Eve Elmore, Masafumi Uchiumi, Jack McArdle, Srikanth Nithyanandam, John F Caruso, Stuart A Best, Lance M Bollinger","doi":"10.1152/ajpregu.00049.2026","DOIUrl":"10.1152/ajpregu.00049.2026","url":null,"abstract":"<p><p>Unilateral lower limb suspension (ULLS) mimics spaceflight-induced decreases in voluntary muscle strength and muscle recruitment. The purpose of this study is to examine the effects of short-term ULLS on quadriceps motor unit action potential train (MUAPT) characteristics during high-intensity isometric contractions. Thirteen healthy adults (7 women and 6 men; age: 18-44 yr) completed bilateral knee extension assessments, including maximal voluntary isometric contraction (MVIC), interpolated twitch, and trapezoidal ramp contractions, before and after 13-day ULLS. Surface electromyography (sEMG) signals from four-pin grid array sensors were decomposed into MUAPTs. Exponential models between MUAPT amplitude and mean firing rate (MFR) and interpulse interval (IPI) standard deviation and linear models between MUAPT amplitude and activation threshold were created for each subjects' limbs pre- and post-ULLS. Limb × time interactions were analyzed using linear mixed models. MVIC (166.6 ± 62.7 vs. 188.9 ± 54.8 Nm, <i>P</i> < 0.001) and voluntary activation (72.5 ± 24.1% vs. 82.0 ± 15.0%, <i>P</i> = 0.018) were significantly reduced in the unloaded limb post-ULLS. Average MUAPT amplitude was not significantly different pre- vs. post-ULLS in either limb (<i>P</i> = 0.322). The exponential function for the MUAPT amplitude MFR relationship and IPI SD relationship was significantly greater post-ULLS in the unloaded limb. Similarly, the slope of the activation threshold was significantly greater in the unloaded limb post-ULLS. Short-term ULLS reduces knee extensor strength and impairs MUAPT characteristics in a size-dependent manner.<b>NEW & NOTEWORTHY</b> Motor unit action potential trains respond differently to disuse based on size of the motor unit during 90% maximal isometric contraction. Small motor units display reduced mean firing after disuse. Large motor units display reduced activation threshold and greater interpulse interval variability.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R33-R43"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013082","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":"Isotocin receptor-adenylyl cyclase signaling mediates pH compensation in marine fish exposed to CO₂-induced acidification.","authors":"Tzu-Yen Liu, Ying-Jey Guh, Yi-An Chen, Shang-Wu Shih, Pei-Hsuan Chou, Yi-Lin Tsou, Yi-Chun Lee, Ruo-Dong Chen, Ming-Yi Chou, Jae-Seong Lee, Pung-Pung Hwang, Marian Y Hu, Yung-Che Tseng","doi":"10.1152/ajpregu.00231.2025","DOIUrl":"10.1152/ajpregu.00231.2025","url":null,"abstract":"<p><p>Marine fish survival is threatened by ocean acidification, but the hormonal mechanisms for pH compensation are not well understood, limiting mechanistic understanding of stress responses in marine fish. We examined isotocin signaling in marine medaka (<i>Oryzias melastigma</i>) exposed to year-2100 ocean acidification conditions (Pco₂ ∼0.14 kPa, pH 7.6). Our analysis demonstrated that isotocin receptor b (ITRb) was selectively upregulated at 6 h postexposure in adult gills, though it showed only a nonsignificant trend at 5 days postfertilization (dpf) embryos, whereas adenylyl cyclase 5 (ADCY5) showed hypercapnia responsiveness primarily at hatching. Using immunofluorescence and confocal microscopy, we found that both ITRb and ADCY5 proteins localize to the basolateral membrane of Na⁺-K⁺-ATPase-positive ionocytes, partially separated from apical H⁺-secretion machinery. Knockdown experiments showed that ITRb-ADCY5 coupling is crucial for pH compensation, with individual knockdown moderately reducing H⁺ secretion and combined knockdown causing severe impairment (>70% reduction) and decreasing transcription of acid-secretion genes (<i>nhe3</i>, <i>ca2</i>, and <i>rhcgb</i>) by 44%-60%. Paradoxically, double knockdown triggered a twofold cAMP increase that failed to restore function, whereas wild-type embryos maintained stable cAMP levels across pH conditions, consistent with the hypothesis that ITRb-ADCY5 coupling may organize cAMP production within specific basolateral microdomains, though direct subcellular imaging would be required to validate this compartmentalization model. The developmental asynchrony between ITRb (5 dpf) and ADCY5 (hatching) responses indicates life-stage-specific vulnerabilities. Our findings reveal that basolateral ITRb-ADCY5 coupling represents a critical control point for pH compensation capacity.<b>NEW & NOTEWORTHY</b> Isotocin signaling, through ITRb-ADCY5 coupling, enables marine fish to compensate for ocean acidification via compartmentalized rather than global cAMP production. Paradoxically, disrupting this pathway doubles cAMP levels yet abolishes H⁺ secretion, revealing that signal localization determines function. The developmental asynchrony between ITRb and ADCY5 responses suggests that pH-stress vulnerabilities are specific to each life stage and require further investigation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R1-R12"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986172","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":"Individuals with posttraumatic stress disorder have increased beat-to-beat blood pressure variability.","authors":"Melissa J McGranahan, Jeann L Sabino-Carvalho, Matias G Zanuzzi, Jeanie Park","doi":"10.1152/ajpregu.00322.2025","DOIUrl":"10.1152/ajpregu.00322.2025","url":null,"abstract":"<p><p>Individuals with posttraumatic stress disorder (PTSD) are at elevated risk for cardiovascular disease (CVD). Emerging research suggests that increased blood pressure variability (BPV) reflects abnormalities in autonomic regulation and may be an early indicator of future CVD risk. PTSD is associated with autonomic dysregulation that is related to PTSD symptoms and is associated with increased risk of CVD; however, BPV in PTSD remains unexplored. We hypothesized that individuals with PTSD would exhibit greater short-term BPV compared with controls and that BPV would correlate with psychological symptoms. Fifty-nine participants (PTSD: <i>n</i> = 38; controls: <i>n</i> = 21) completed beat-to-beat blood pressure recordings via finger photoplethysmography for 5-10 min. BPV indices included standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure. PTSD symptoms were assessed via the PTSD checklist, fifth edition. Anxiety symptoms were assessed via the State-Trait Anxiety Inventory, and depression symptoms were assessed via Beck's Depression Inventory. Compared with controls, the PTSD group had significantly higher SBP-SD (4.3 ± 1.7 vs. 3.3 ± 1.3 mmHg, <i>P</i> = 0.021), SBP-CV (3.7 ± 1.6 vs. 2.7 ± 1.0 mmHg, <i>P</i> = 0.005), and DBP-CV (4.6 ± 1.4 vs. 3.9 ± 1.4 mmHg, <i>P</i> = 0.045). No group differences were found in ARV measures or cardiac baroreflex sensitivity. BPV was not significantly correlated with PTSD, anxiety, or depression symptoms. In conclusion, individuals with PTSD exhibited greater BPV, but psychological symptoms were not associated with BPV indices.<b>NEW & NOTEWORTHY</b> Individuals with PTSD have higher resting beat-to-beat BPV compared with healthy controls, despite no differences in average blood pressure values. Elevated systolic and diastolic BPV indices showed moderate-to-large effect sizes. BPV indices were not associated with PTSD, anxiety, or depression symptoms. These findings suggest that increased BPV in individuals with PTSD may reflect altered cardiovascular regulation relevant to heightened cardiovascular risk.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R13-R22"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986174","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":"Ruby-throated hummingbirds suppress ATP demand to save energy during torpor.","authors":"Amalie J Hutchinson, Cory R Elowe, James F Staples, Christopher G Guglielmo","doi":"10.1152/ajpregu.00071.2026","DOIUrl":"10.1152/ajpregu.00071.2026","url":null,"abstract":"<p><p>Ruby-throated hummingbirds are heterothermic and enter torpor at night to save energy. We recently investigated the ATP supply pathway through mitochondria as a mechanism for whole animal metabolic rate suppression observed in torpor, but found, unlike heterothermic mammals, mitochondrial function is not actively suppressed in torpid hummingbirds. In this study, we tested the hypothesis that the inhibition or downregulation of major ATP-consuming enzymes (SERCA and Na⁺/K⁺ ATPase) is involved in whole animal metabolic rate suppression in torpid hummingbirds. Specific SERCA activity in the pectoralis muscle did not change between torpor and normothermia, but the phosphorylation of the \"uncoupling\" protein sarcolipin (SLN) increased by 14% in torpor. This indicates a downregulation of ATP demand and reduced heat generation as a possible mechanism of metabolic suppression. Na⁺/K⁺ ATPase-specific enzyme activity was 43% lower in torpor than in normothermia, although the phosphorylation state of the enzyme was unchanged. Taken together, we suggest that hummingbirds suppress pathways of ATP demand during torpor as a mechanism to drive metabolic rate suppression in concert with passive metabolic suppression initiated by adjusting thermoregulation and allowing core body temperature to decrease.<b>NEW & NOTEWORTHY</b> The cellular mechanisms that underlie hummingbird torpor are only beginning to be studied. We are the first to report two ATP-demand pathways downregulated in torpid ruby-throated hummingbirds. We characterized SERCA and Na⁺/K⁺ ATPase activity in normothermia and torpor. SERCA activity was 10-13× higher than in songbirds. Sarcolipin was more phosphorylated in torpor, reducing heat production, and Na⁺/K⁺ ATPase activity fell 43%. These shifts lower ATP demand and conserve energy during torpor.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R53-R62"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136205","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":"α-Adrenergic regulation of blood pressure in acclimatizing lowlanders and Andean highlanders at high altitude.","authors":"Emily R Vanden Berg, Graham M Fraser, Andrew R Steele, Victoria L Meah, Lydia L Simpson, Lindsey F Berthelsen, Stephen A Busch, Michael M Tymko, Gustavo A Vizcardo-Galindro, Rómulo J Figueroa-Mujíca, Francisco C Villafuerte, Philip N Ainslie, Mike Stembridge, Jonathan P Moore, Craig D Steinback","doi":"10.1152/ajpregu.00164.2025","DOIUrl":"10.1152/ajpregu.00164.2025","url":null,"abstract":"<p><p>Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g., augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to <i>1</i>) resting systemic sympathetic transduction and <i>2</i>) pressor responses to sympathoexcitation in acclimatizing lowlanders (9 M and 4 F) and Andean highlanders (15 M) at 4,300 m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α₁-adrenergic agonist (phenylephrine) before and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041 ± 0.0037 to 0.0017 ± 0.0017 mmHg·%^-1, <i>P</i> = 0.026) and highlanders (0.0033 ± 0.0024 to 0.0008 ± 0.0007 mmHg·%^-1, <i>P</i> = 0.005) under α-adrenergic blockade (main effect <i>P</i> < 0.001) and was not different between groups (main effect <i>P</i> = 0.276). However, pressor responses to apnea (lowlanders, +25 ± 5 mmHg and highlanders, +22 ± 7 mmHg) were unchanged following phentolamine (lowlanders, +25 ± 8 mmHg and highlanders, +20 ± 8 mmHg; main effect <i>P</i> = 0.174) despite unchanged MSNA responses between conditions (main effect <i>P</i> = 0.162). Highlanders exhibited reduced MSNA responses compared with lowlanders regardless of condition (main effect <i>P</i> = 0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.<b>NEW & NOTEWORTHY</b> This study provides insight into the mechanisms involved in the sympathetic control of blood pressure at rest and in response to autonomic stress in different populations at high altitude. We demonstrate that resting blood pressure regulation is mediated primarily through α-adrenergic mechanisms in both lowlanders and Indigenous Andean highlanders at high altitude. However, pressor responses to apneic stress appear to be regulated by an alternative mechanism, particularly in highlanders who require less sympathetic activation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R86-R101"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161450","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}