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

{"title":"Low-load blood flow restriction training and ischemia modulate expression of Na⁺,K⁺-ATPase and FXYDs in human skeletal muscle.","authors":"Vid Jan, Katarina Miš, Alan Kacin, Anja Vidović, Tina Tomc Žargi, Klemen Stražar, Matej Podbregar, Tomaž Marš, Matej Drobnič, Alexander V Chibalin, Sergej Pirkmajer","doi":"10.1152/ajpregu.00340.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00340.2025","url":null,"abstract":"<p><p>Anterior cruciate ligament (ACL) rupture leads to muscle deconditioning and downregulation of Na⁺,K⁺-ATPase (NKA). Low-load blood flow restriction (LL-BFR) training was shown to improve muscle function after ACL injury, but its effects on NKA are unknown. We analysed expression of NKA and its FXYD regulators in knee muscles from ACL-injured subjects undergoing LL-BFR, low-load training with sham blood flow restriction (LL-Sham), or no training (Control). Additionally, we dissected effects of ischemia components by subjecting cultured human myotubes to glucose deprivation and/or hypoxia. The LL-BFR group had higher vastus lateralis mRNA levels of NKAα1 than the Control and LL-Sham groups. In vitro, NKAα1, NKAβ1, and NKAβ3 mRNA and NKAα1 and NKAβ1 protein levels were downregulated by sustained ischemia and glucose deprivation, but not hypoxia, while FXYD5 protein was upregulated by glucose deprivation. Conversely, intermittent ischemia had no effect on NKA or FXYD expression. In conclusion, LL-BFR training was associated with upregulation of NKAα1 mRNA levels in the vastus lateralis after ACL injury; however, in the absence of corresponding changes in protein abundance, its contribution to functional recovery remains unclear. Moreover, our in vitro findings suggest that glucose availability plays a major role in modulating NKA and FXYD expression in muscle cells under ischemic conditions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878699","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":"Changes in IMCL content and storage characteristics during an acute bout of high-intensity interval exercise are influenced by sex and muscle fiber type.","authors":"Megan M Lo, Kayleigh M Beaudry, Claire Woodgate, Michaela C Devries","doi":"10.1152/ajpregu.00282.2025","DOIUrl":"10.1152/ajpregu.00282.2025","url":null,"abstract":"<p><p>Recently it was reported that intramyocellular lipids (IMCL) do not contribute to energy production during high-intensity interval exercise (HIIE) in males. However, females rely to a greater extent on lipid during moderate-intensity exercise compared with males, thus perhaps IMCL contribute to energy production during HIIE in females. The purpose of this study is to determine whether sex influences IMCL use or IMCL storage characteristics during an acute bout of HIIE. Young, healthy, recreationally active males (<i>n</i> = 12) and females (<i>n</i> = 12) performed an acute bout of HIIE (10 × 1 min at 90%HRmax) with biopsies taken from vastus lateralis prior to and following exercise for electron microscopic determination of IMCL storage and Western blot analysis of proteins related to lipid and aerobic metabolism. Total energy expenditure and relative contributions of fat and carbohydrate oxidation were determined using indirect calorimetry. Though carbohydrate oxidation was greater in males (males: 2.49 g/min, females: 1.69 g/min, <i>P</i> < 0.0001) during exercise, there were no sex differences in fat oxidation (males: 0.045 g/min, females: 0.049 g/min, <i>P</i> = 0.99). Sex influenced changes in the peripheral intermyofibrillar (IMF) region of type II fibers with IMCL content decreasing by 28% in females but increasing by 26% in males (<i>P</i> = 0.049), whereas the proportion of IMCL-mitochondria apposition increased by 26% in females compared with only 3% in males (<i>P</i> = 0.03). We also report differences in the change in IMCL morphology that are consistent with altered IMCL handling and mitochondrial interaction in females. We identify novel, sex-specific changes in IMCL content, apposition with mitochondria and morphology during an acute bout of HIIE.<b>NEW & NOTEWORTHY</b> To our knowledge, this is the first study to comprehensively examine sex-based differences in changes in intramyocellular lipid (IMCL) content, morphology, and mitochondrial interaction following acute high-intensity interval exercise (HIIE). We report that sex influences changes in IMCL content, morphology, and apposition with mitochondria during HIIE. Our findings provide novel microscopic insights into sex-specific IMCL organization and mitochondrial interaction during HIIE, and highlight the importance of considering sex in investigations of skeletal muscle metabolism.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R347-R363"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373765","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":"Seven days of warm water immersion modulate baseline fluid-regulatory hormones without altering acute multisystem physiological stress responses in older males.","authors":"Ben J Lee, James J McCormick, Kelli E McCormick, Kristina-Marie T Janetos, Glen P Kenny","doi":"10.1152/ajpregu.00099.2026","DOIUrl":"10.1152/ajpregu.00099.2026","url":null,"abstract":"<p><p>Older adults exhibit heightened vulnerability to heat-related morbidity, yet it remains unclear whether short-term heat acclimation modifies integrative physiological stress responses in aging. We tested whether 7 days of passive heat acclimation via warm water immersion alters basal concentrations and acute exercise-heat stress responses of biomarkers reflecting fluid regulation, gastrointestinal epithelial integrity, renal stress, and inflammation in older males. Twelve habitually active older males (median [interquartile range] age: 68 [64-73] yr; [Formula: see text]: 34.1 [29.4-36.1] mL O₂·kg^-1·min^-1) completed an exercise-heat stress test before and after 7 consecutive days of warm water immersion (∼40°C), with rectal temperature maintained at ∼38.5°C for the final 60 min. Blood samples were collected before and after each exercise-heat stress test and analyzed using linear mixed-effects models (day × time). Repeated warm water immersion increased resting renin by 68% [95% confidence interval: 29, 120; <i>P</i> < 0.001], whereas neutrophil gelatinase-associated lipocalin and lipopolysaccharide-binding protein decreased by 24% [-40, -4; <i>P</i> = 0.023] and 22% [-37, -3; <i>P</i> = 0.026], respectively. Exercise-heat stress increased aldosterone by 45% [12, 87%; <i>P</i> = 0.004], renin by 41% [8, 84%; <i>P</i> = 0.01], intestinal fatty acid-binding protein by 52% [26, 85%; <i>P</i> < 0.001], and plasma osmolality by 5.6% [2.5, 8.7%; <i>P</i> < 0.001]. However, there was no day × time interaction for any biomarker (all <i>P</i> > 0.05), indicating that 7 days of warm water immersion did not alter the magnitude of the exercise-heat stress response. Short-term passive heat acclimation in older males induces selective fluid-regulatory endocrine adaptations consistent with preserved renin-angiotensin-aldosterone system plasticity, whereas gastrointestinal and renal stress responses to exercise-heat exposure remain unchanged.<b>NEW & NOTEWORTHY</b> This study demonstrates that short-term (7 days) passive heat acclimation via warm water immersion induces selective endocrine adaptation without uniform protection across physiological systems in older males aged 60-80. Although RAAS-mediated fluid regulation was modified following heat acclimation, gastrointestinal and renal stress responses to acute heat exposure persisted. These findings suggest that physiological adaptation to repeated heat exposure in aging may be compartmentalized across organ systems, with implications for vulnerability during extreme heat events.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R364-R375"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629375","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":"Stretching our understanding: is the human mechanoreflex more than a small, transient contributor to sympathetic regulation?","authors":"Seth W Holwerda","doi":"10.1152/ajpregu.00151.2026","DOIUrl":"10.1152/ajpregu.00151.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R387-R389"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688335","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":"Systematic understanding of acute effects of dexmedetomidine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation.","authors":"Midori Kakuuchi, Toru Kawada, Nana Hiraki, Masafumi Fukumitsu, Kei Sato, Taichi Ando, Kazunori Uemura, Yoshihiro Muragaki, Kunihiko Kiuchi, Joe Alexander, Keita Saku","doi":"10.1152/ajpregu.00150.2026","DOIUrl":"10.1152/ajpregu.00150.2026","url":null,"abstract":"<p><p>Dexmedetomidine (DEX) is a centrally acting α₂-adrenergic agonist widely used for sedation in emergency and intensive care settings. We examined the effects of DEX on baroreflex-mediated sympathetic regulation of arterial pressure (AP) to distinguish its central and peripheral effects. In anesthetized male Wistar-Kyoto rats (<i>n</i> = 8), baroreflex-mediated changes in sympathetic nerve activity (SNA), AP, and heart rate (HR) were evaluated before and after intravenous DEX administration. DEX (2.5 μg/kg) significantly reduced the response ranges of AP (64.4 ± 9.2 to 5.8 ± 3.0 mmHg; <i>P</i> < 0.001), HR (46.5 ± 23.2 to 5.0 ± 6.2 beats/min; <i>P</i> = 0.003), and SNA (87.0 ± 7.5% to 12.6 ± 8.2%; <i>P</i> < 0.001). DEX also decreased the lower limits of HR (325.9 ± 14.6 to 302.2 ± 16.3 beats/min; <i>P</i> < 0.001) and SNA (14.6 ± 6.1% to 1.8 ± 3.0%; <i>P</i> = 0.037) but increased the lower limit of AP (65.4 ± 7.5 to 72.6 mmHg; <i>P</i> = 0.026). Furthermore, DEX reduced both the operating-point AP and gain. Peripheral effects contributed to an increase in operating-point AP (61.7 ± 9.1 vs. 80.9 ± 9.7 mmHg; <i>P</i> = 0.045) but did not affect operating-point gain (0.05 ± 0.08 vs. 0.05 ± 0.08; <i>P</i> = 0.859). In summary, DEX markedly suppressed SNA and induced peripheral vasoconstriction. These peripheral effects contributed to increased minimal AP and preservation of operating-point AP. However, the operating-point gain was substantially reduced, suggesting that AP stability in response to exogenous disturbances may be compromised under DEX sedation.<b>NEW & NOTEWORTHY</b> Dexmedetomidine profoundly reshapes baroreflex control beyond its sedative effects. In rats, it markedly reduced the response ranges of arterial pressure, heart rate, and sympathetic nerve activity, while increasing the minimum arterial pressure, a finding consistent with peripheral vasoconstriction. Although these peripheral effects helped preserve operating-point arterial pressure, baroreflex gain was substantially attenuated, suggesting that arterial pressure stability against exogenous disturbances may be compromised during dexmedetomidine sedation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R427-R434"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688386","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":"Relationships between plasma volume, fluid regulatory hormones, and maximal oxygen uptake following fixed-workload heat acclimation in men and women.","authors":"Andrew M Greenfield, Shaun C Brazelton, Billie K Alba, Phillip O Bodurtha, K Riley Connor, Nisha Charkoudian, Benjamin A Fry, Samantha J Goldenstein, Thomas A Mayer, David H Gonzalez-Rojas, Benjamin J Ryan, Afton D Seeley, MariaLena A Shaw, Roy M Salgado, Gabrielle E W Giersch","doi":"10.1152/ajpregu.00274.2025","DOIUrl":"10.1152/ajpregu.00274.2025","url":null,"abstract":"<p><p>Plasma volume (PV) expansion may support various adaptations associated with heat acclimation (HA), including a potential increase in temperate maximal oxygen uptake (V̇o_2max). The PV response to HA is highly variable, and mechanisms that contribute to this variability are poorly understood, including the potential influence of sex. Twenty-six volunteers (11 M; 15 F) underwent a 10-day HA program that consisted of 120 min of fixed-workload treadmill exercise at 40°C and 40% relative humidity (RH). Temperate (∼20°C) V̇o_2max and PV (carbon monoxide rebreathing) were measured before and after HA. Serum aldosterone, estradiol, and progesterone, as well as plasma copeptin, were measured on the first and last day of HA. HA was successfully induced, as evidenced by reductions in body core temperature, heart rate, and increased sweating rate during exercise in the heat. PV (Pre: 3,280 ± 552 mL, Post: 3,380 ± 685 mL; <i>P</i> = 0.096) and V̇o_2max (3.06 ± 0.82 L/min, 3.09 ± 0.77 L/min; <i>P</i> = 0.453) were unchanged with HA at the cohort level, and sex did not modify responses to HA (interaction effects: <i>P</i> > 0.05). ΔAldosterone was correlated with ΔPV (<i>P</i> = 0.047, <i>r</i> = 0.393, <i>r</i>² = 0.155) and Δprogesterone with ΔPV in women (<i>P</i> = 0.039, <i>r</i> = 0.537, <i>r</i>² = 0.289). In our young, healthy cohort of men and women, PV and V̇o_2max were unchanged after fixed-workload HA, and the overall adaptive response did not differ based on sex. The PV response was highly variable across individuals such that increases in PV were not observed in most individuals. Interindividual variability in circulating progesterone may contribute to some of the response in women.<b>NEW & NOTEWORTHY</b> We provide the first direct assessment of the plasma volume (PV) and volume regulatory responses to a practical, fixed-workload heat acclimation (HA) protocol in men and women. Maximal oxygen uptake was not influenced by HA, sex, or individual changes in PV. In women, progesterone was correlated with PV changes following HA.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R435-R445"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688348","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":"The growth of developing oocytes and hypothalamus-pituitary-ovary functions in goldfish under absolute food deprivation.","authors":"Vahidehalsadat Mirjalili, Negar Kazori, Sayyed Mohammad Hadi Alavi, Mahdi Golshan, Azadeh Hatef, Magdalena Socha, Sylvain Milla, Suraj Unniappan, Otomar Linhart","doi":"10.1152/ajpregu.00034.2026","DOIUrl":"10.1152/ajpregu.00034.2026","url":null,"abstract":"<p><p>Food deprivation (FD) seriously affects puberty onset and oogenesis in female fishes. It has been suggested that meal-responsive peptides interact with hypothalamus-pituitary-ovary (HPO) functions; however, current knowledge regarding the integration of metabolism with reproduction remains inconclusive. In the present study, we investigated the effects of 7 days absolute FD on the reproductive system of adult female goldfish (<i>Carassius auratus</i>). The number of nonvitellogenic oocytes was higher in the food-deprived goldfish than in fed goldfish, whereas the number of vitellogenic oocytes was lower (<i>P</i> < 0.05). However, FD had no effects on gonadosomatic index, ovarian reserve, oocyte diameter at different growth stages, and circulating levels of 17-β estradiol and testosterone. Analysis of hypothalamus-pituitary hormones revealed no significant changes in <i>kiss1</i>, <i>gprg54</i>, or <i>gnrh3</i> mRNA levels in the food-deprived goldfish, whereas circulating luteinizing hormone (Lh) level was increased (<i>P</i> < 0.05). These findings suggest that the FD-induced increase in Lh level was not mediated by activation of the Kiss-Gnrh system. Ovarian transcript of ghrelin <i>O</i>-acyltransferase (<i>goat</i>) mRNA, which encodes the enzyme that octanoylates ghrelin, was also increased in the food-deprived goldfish, along with decreases in hepatosomatic and viscerosomatic indices. Taken together, our results show that FD inhibits the growth of developing oocytes along with enhancement of posttranslational modification of ghrelin in the ovary. This study provides novel insight into the integration of metabolic signals with HPO hormones in the female fish.<b>NEW & NOTEWORTHY</b> Food deprivation (FD) seriously interferes with the female reproductive system. Our findings show FD-inhibited growth of developing oocytes along with decrease in hepatosomatic index, and increase in the ovarian <i>goat</i> mRNA encoding the enzyme for the acyl-modification of ghrelin. Sex steroid levels and <i>kiss1</i>, <i>gpr54</i>, and <i>gnrh3</i> mRNAs remained unchanged, whereas circulating Lh was increased under FD. This study provides novel information to better elucidate integrative physiology of hypothalamus-pituitary-ovary with oocyte growth under FD.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R324-R335"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468411","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":"Influence of lowered muscle temperature upon postexercise hemodynamics.","authors":"Brianna Rowe, Phillip Tracy, John Frerichs, Nathan B Morris, James Pearson","doi":"10.1152/ajpregu.00107.2026","DOIUrl":"10.1152/ajpregu.00107.2026","url":null,"abstract":"<p><p>Our aim was to test the hypothesis that independently lowering muscle tissue temperature would attenuate postexercise increases in leg vascular conductance and decreases in arterial blood pressure. Eleven participants (4 females; age, 27 ± 6 yr; height, 176 ± 10 cm; weight, 72.8 ± 11.3 kg; and V̇o_2max 39.34 ± 7.69 mLO₂·kg·min) completed three trials wherein they donned a water-perfused suit and exercised for 60-min at 60% V̇o_2max followed by 60-min supine recovery. Different water-circulation protocols were used to either maintain normal skin and muscle temperatures throughout recovery (normothermic), lower skin and muscle temperatures during recovery (cold), or lower muscle temperature but rewarm the skin temperature back to normal during recovery (rewarming). Internal (Tcore), skin (Tskin), and muscle temperatures (Tmuscle), mean arterial pressure, leg and cutaneous vascular conductance's were measured. Tcore was not different between trials (<i>P</i> > 0.05). Throughout the final 15 min of recovery, Tmuscle was lower (60 min: 35.94 ± 0.83°C vs. 36.74 ± 0.27°C, <i>P</i> < 0.05), but Tskin was not different (60 min: 33.8 ± 0.5°C vs. 33.9 ± 0.5°C, <i>P</i> > 0.05) in the rewarming relative to the normothermic trial. However, mean arterial pressure, leg vascular conductance, and cutaneous vascular conductance were not different between normothermic and rewarming trials (all <i>P</i> > 0.05). The findings suggest that independently lowering muscle tissue temperature after exercise does not alter whole leg vascular conductance or decreases in arterial blood pressure.<b>NEW & NOTEWORTHY</b> Our aim was to independently examine the influence of lowered muscle temperature upon leg vascular conductance and arterial blood pressure following exercise in cold or thermoneutral environments when skin and core temperatures and cutaneous vascular conductance were similar. These findings indicate that independent reductions in muscle temperature following exercise do not alter whole leg vascular conductance or postexercise arterial blood pressure when skin temperature and cutaneous vascular conductance are normal.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R336-R346"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468364","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":"Sympathetic action potential synchronicity and blood pressure regulation in healthy young adults.","authors":"Nathaniel J Iannarelli, Julia E Spafford, Cameron M Lynn, Stephen S Cheung, Deborah D O'Leary, J Kevin Shoemaker, Stephen A Klassen","doi":"10.1152/ajpregu.00082.2026","DOIUrl":"10.1152/ajpregu.00082.2026","url":null,"abstract":"<p><p>This study investigated sympathetic neural blood pressure regulation in humans by quantifying synchronous and asynchronous action potential (AP) discharge. Muscle sympathetic AP discharge was measured (microneurography; continuous wavelet transform) in 21 healthy young adults. Baroreflex functions (central baroreflex component) and diastolic blood pressure (DBP) transduction (peripheral baroreflex component) were quantified for synchronous and asynchronous AP discharge. Analyses were stratified by falling and rising blood pressures to examine hysteresis. Medium-sized synchronous APs exhibited the greatest discharge frequencies (<i>P</i> < 0.001) and baroreflex threshold gains (<i>P</i> < 0.001). Asynchronous AP discharge exhibited weak baroreflex regulation (<i>P</i> = 0.999). Central baroreflex regulation of medium-sized synchronous APs exhibited hysteresis. Medium-sized synchronous APs expressed stronger baroreflex threshold gains (sympathetic AP cluster 3: DBP Fall slope: -5.48 ± 3.07%/mmHg, DBP Rise slope: -4.71 ± 2.91%/mmHg; <i>P</i> < 0.001) and greater discharge frequencies (sympathetic AP cluster 3: DBP Fall: 0.29 ± 0.15 Hz, DBP Rise: 0.25 ± 0.13 Hz; <i>P</i> < 0.001) during falling compared with rising blood pressures. The peripheral baroreflex component exhibited hysteresis. Transduction responses to synchronous AP discharge were larger during rising compared with falling blood pressures (DBP Fall peak: 2.67 ± 1.02 mmHg, DBP Rise peak: 3.14 ± 1.29 mmHg; <i>P</i> = 0.009). Asynchronous AP discharge was associated with attenuated blood pressure reductions compared with cardiac cycles with no AP activity, and more so during rising compared with falling blood pressures (DBP Fall nadir: -2.17 ± 1.09 mmHg, DBP Rise nadir: -1.43 ± 0.68 mmHg; <i>P</i> < 0.001). These data suggest that homeostatic blood pressure regulation is achieved via distinct subpopulations of synchronous and asynchronous APs that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral baroreflex hysteresis may reflect a moment-to-moment compensatory strategy for blood pressure regulation.<b>NEW & NOTEWORTHY</b> This study found that <i>1</i>) medium-sized synchronous APs exhibit central and peripheral baroreflex hysteresis and <i>2</i>) despite negligible baroreflex regulation, asynchronous APs attenuate reductions in blood pressure during cardiac cycles with no synchronous AP activity. These findings suggest that blood pressure regulation is achieved via subpopulations of synchronous and asynchronous postganglionic neurons that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral sympathetic baroreflex hysteresis may reflect a moment-to-moment compensatory strategy regulating blood pressure.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R390-R401"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668203","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":"Time matters: BMAL1 and cardiovascular-kidney-metabolic health.","authors":"Lance Dylan Reynolds, Zhengrong Guan, Jennifer S Pollock","doi":"10.1152/ajpregu.00041.2026","DOIUrl":"10.1152/ajpregu.00041.2026","url":null,"abstract":"<p><p>Modern lifestyles increasingly promote unhealthy eating behaviors, contributing to the global rise in cardiovascular-kidney-metabolic diseases (CKMD). Circadian rhythms, anticipatory responses that coordinate biological processes with the 24-h rotation of the earth, are tightly linked to feeding behavior and nutrient metabolism, which are crucial for cardiovascular-kidney-metabolic homeostasis. At the molecular level, core circadian \"clock genes\" take part in a highly-conserved, regulatory feedback loop that optimizes metabolic processes for the anticipated time of food intake. Among the molecular components of the circadian clock, the transcription factor brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) plays a central role in coordinating metabolic functions. Notably, BMAL1 and feeding behavior are at the intersection of circadian biology and metabolism, regulating each other. In this review, we summarize recent insights in metabolic physiology from global and tissue-specific <i>Bmal1</i> knockout animal models, highlighting how BMAL1 influences CKMD consequences in response to dietary composition and feeding schedules and whether sex is a determinant in these outcomes. We also discuss the potential of molecular clock-targeted therapies for CKMD. Maintaining circadian integrity is central to mitigating CKMD; thus, modulating clock-regulated pathways may offer novel therapeutic strategies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R469-R491"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672966","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}