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

{"title":"Effect of pre-exercise dietary nitrate on skeletal muscle blood flow in a rat model of pulmonary hypertension.","authors":"Gary Marshall Long, Ashley D Giourdas, Amanda J Fisher, Tim Lahm, Andrew R Coggan, Mary Beth Brown","doi":"10.1152/ajpregu.00037.2025","DOIUrl":"10.1152/ajpregu.00037.2025","url":null,"abstract":"<p><p>Skeletal muscle dysfunction contributes to exercise intolerance in patients with pulmonary arterial hypertension (PAH). Reduced blood flow to skeletal muscle has been demonstrated in a rat model of the disease. We investigated the effect of acute nitrate ([Formula: see text]) ingestion via beetroot juice (BRJ) on exercising muscle blood flow, and on plasma and muscle nitrate ([Formula: see text]), nitrite ([Formula: see text]), and cyclic GMP (cGMP) in male Sprague Dawley rats (∼200 g, <i>n</i> = 24) with monocrotaline-induced (60 mg/kg) pulmonary hypertension (PH). Muscle blood flow was assessed at rest and during treadmill running using fluorescent microspheres. Despite higher plasma [Formula: see text] (756 ± 118 vs. 63 ± 22 µmol/L, <i>P</i> ≤ 0.001) and [Formula: see text] (0.63 ± 0.10 vs. 0.24 ± 0.04 µmol/L, <i>P</i> = 0.003), no difference between BRJ and PL was observed in either resting (<i>P</i> = 0.88) or exercising (<i>P</i> = 0.42) blood flow. Only [Formula: see text] was higher in BRJ vs. PL for both the soleus (sol: 261 ± 20 vs. 123 ± 18 vs. µmol/kg, <i>P</i> ≤ 0.0005) and vastus lateralis (VL: 176 ± 34 vs. 86 ± 14 µmol/kg, <i>P</i> = 0.02), with no differences for [Formula: see text] (sol: 1.9 ± 0.2 vs. 1.7 ± 0.3 µmol/kg, <i>P</i> = 0.49; VL: 1.04 ± 0.2 vs. 1.03 ± 0.2 µmol/kg, <i>P</i> = 0.97) or cGMP (sol: 4.8 ± 2.1 vs. 3.9 ± 1.5 vs. nmol/kg, <i>P</i> = 0.22; VL 6.0 ± 3.8 vs. 5.8 ± 3.2 nmol/kg, <i>P</i> = 0.91). In a rat model of severe PH, acute BRJ dosing increases circulating and muscle [Formula: see text] but does not alter muscle blood flow. Absence of change in muscle [Formula: see text] and cGMP suggest insufficiently altered downstream NO signaling with BRJ supplementation.<b>NEW & NOTEWORTHY</b> Muscle dysfunction in pulmonary hypertension (PH) includes impairment in blood flow. The use of dietary nitrate to increase blood flow and potentially improve exercise tolerance has not been studied in this population. We show that acute dietary nitrate supplementation does not increase directly measured muscle blood flow in a PH rat, despite increases in plasma nitrate and nitrite. Muscle nitrate is elevated, but other markers of nitric oxide signaling (nitrite and cyclic GMP) are unaltered.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R317-R325"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537772","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":"Unlocking the gut: microbiome's role in energy metabolism.","authors":"Neil B Blok, Nadejda Bozadjieva-Kramer","doi":"10.1152/ajpregu.00158.2025","DOIUrl":"10.1152/ajpregu.00158.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R326-R328"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599143","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":"Serotonin neurons are necessary for tonic sodium intake inhibition.","authors":"Silvia Gasparini, Gordon F Buchanan, Joel C Geerling","doi":"10.1152/ajpregu.00029.2025","DOIUrl":"10.1152/ajpregu.00029.2025","url":null,"abstract":"<p><p>Sodium appetite is a motivated behavior that occurs in response to sodium deprivation. Various neurotransmitters, including serotonin, are thought to regulate sodium intake. In the present study, we used genetic deletion to test whether serotonergic neurons are necessary for regulating sodium appetite. First, we confirmed that <i>Pet1</i>-Cre;<i>Lmx1b</i>^flox/flox (<i>Lmx1b</i>^f/f/p) mice have nearly complete deletion of serotonergic neurons, with only sporadic cells remaining. Next, we measured baseline intake of water and 3% NaCl and found that <i>Lmx1b</i>^f/f/p mice consume more salt than Cre-negative littermate-control mice (<i>Lmx1b</i>^f/f). Finally, we tested the necessity of serotonergic neurons for thirst and sodium appetite inhibition. After 24-h water deprivation, mice lacking serotonergic neurons exhibited an intact thirst response by increasing water intake just like Cre-negative littermates. After furosemide diuresis followed by 24-h sodium deprivation, mice lacking serotonergic neurons exhibited an intact sodium appetite response by increasing salt and water intake like Cre-negative littermates. Interestingly, the baseline daily salt intake of <i>Lmx1b</i>^f/f/p mice increased between tests relative to their initial baseline. Together, these findings indicate that although serotonergic neurons are not the primary mechanism controlling sodium appetite, they act as a \"brake,\" limiting sodium consumption. This tonic inhibitory role may protect against excess sodium intake and suggests the possibility that serotonergic medications may influence dietary sodium consumption.<b>NEW & NOTEWORTHY</b> This study demonstrates a fundamental role for serotonergic neurons in limiting sodium intake. Mice with genetic deletion of serotonin-producing neurons consume more salt, indicating that serotonergic neurons act like a brake to restrain sodium appetite. These findings advance our understanding of how the brain controls salt-seeking behavior.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R258-R271"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482845","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":"Midlife estradiol treatment reduces the firing rate of liver-related PVN neurons in ovariectomized high-fat diet-fed mice.","authors":"Adrien J R Molinas, Lucie D Desmoulins, Courtney M Dugas, Gabrielle L Williams, Sophie Kamenetsky, Viviane Felintro de Souza, Matthieu J Maroteaux, Roslyn K Davis, Jill M Daniel, Laura A Schrader, Andrea Zsombok","doi":"10.1152/ajpregu.00117.2025","DOIUrl":"10.1152/ajpregu.00117.2025","url":null,"abstract":"<p><p>Estrogen plays a critical role in the regulation of physiological functions, including metabolism, and its involvement in the regulation of insulin sensitivity and glucose homeostasis has major clinical relevance. Despite the importance of the brain-liver pathway in the regulation of glucose metabolism and that postmenopausal women have an increased risk of developing metabolic disorders, the effect of hormone therapy on hypothalamic neurons involved in the regulation of liver metabolism is not known. Here, we tested the hypothesis that in middle-aged, high-fat diet (HFD)-fed female mice, the excitability of liver-related neurons in the paraventricular nucleus (PVN) of the hypothalamus is increased, whereas estradiol treatment attenuates this increase. Mice fed with phytoestrogen-free control (low-fat diet) or HFD were ovariectomized, received a silastic capsule implant containing either estradiol or vehicle, and stayed on their respective diets. Estradiol treatment resulted in less fat mass and lower body weight. Liver-related neurons were identified with a retrograde, transsynaptic viral tracer, and patch-clamp recordings were conducted from identified neurons in the PVN. Our data show that the excitability of liver-related PVN neurons was increased in ovariectomized HFD mice compared with LFD-fed mice. In estradiol-treated HFD mice, the firing of liver-related PVN neurons was significantly reduced compared with vehicle-treated HFD mice, whereas in LFD mice, estradiol treatment did not alter the activity of liver-related PVN neurons. Our findings suggest that midlife estradiol treatment has beneficial effects on liver-related PVN neurons and thus may contribute to the improved metabolic status observed in estradiol-treated HFD mice.<b>NEW & NOTEWORTHY</b> Menopause increases the risk of metabolic disorders, and despite the importance of the brain-liver pathway in the regulation of glucose homeostasis, the effect of estradiol treatment on liver-related neurons is not known. Our data show that in middle-aged, high-fat diet-fed, ovariectomized female mice, the excitability of liver-related neurons in the paraventricular nucleus is increased, whereas estradiol treatment attenuates this increase. These data suggest that midlife estradiol treatment is beneficial for the brain-liver pathway.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R245-R252"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493449","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":"The hyperemic response to exercise is blunted in females with polycystic ovary syndrome.","authors":"Will Huckins, Shannon I Delage, Danielle E Berbrier, Derek A Skolnik, Hana Sandra Aiko Keightley, Charlotte W Usselman","doi":"10.1152/ajpregu.00263.2024","DOIUrl":"10.1152/ajpregu.00263.2024","url":null,"abstract":"<p><p>Some beneficial adaptations to exercise training appear to be blunted in females with polycystic ovary syndrome (PCOS) relative to controls. Impaired hyperemic responses to exercise may contribute to this phenomenon. Therefore, we compared the active limb hyperemic response with acute dynamic single-leg exercise to exhaustion between lean females with PCOS [<i>n</i> = 14, age: 23 ± 5 yr, body mass index (BMI): 23 ± 2 kg/m²] and age- and BMI-matched females without PCOS (CTRL; <i>n</i> = 14). Femoral artery blood flow (FBF; duplex vascular ultrasound) and finger photoplethysmography-derived mean arterial blood pressure (MAP) were recorded at baseline and throughout graded concentric knee extensions to exhaustion (Biodex Pro 4 dynamometer). Resting FBF was not different between PCOS and CTRL (416 ± 238 vs. 360 ± 163 mL/min, respectively; <i>P</i> = 0.43). FBF and leg vascular conductance responses to exercise were blunted in PCOS relative to CTRL (effects of group: <i>P</i> = 0.03 and 0.02, respectively). Resting MAP was higher in PCOS than CTRL (91 ± 6 vs. 86 ± 7 mmHg; <i>P</i> = 0.04), although MAP responses to exercise were not different between PCOS and CTRL overall (effect of group: <i>P</i> = 0.31). In sum, we observed blunted hyperemic responses throughout exercise in this cohort of relatively healthy females with PCOS.<b>NEW & NOTEWORTHY</b> We studied a young and lean cohort of females with PCOS to determine whether acute hyperemic responses to exercise would be adversely impacted by PCOS, even in a relatively healthy cohort. Despite similar blood pressure responses to exercise, acute hyperemic responses to single-leg exercise to exhaustion were smaller in PCOS than controls. This provides novel information in an attempt to understand the cardiovascular dysfunction characteristic of females with PCOS.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R297-R307"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599130","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":"Modeling calcium and magnesium balance: effects of diuretics.","authors":"Pritha Dutta, Anita T Layton","doi":"10.1152/ajpregu.00031.2025","DOIUrl":"10.1152/ajpregu.00031.2025","url":null,"abstract":"<p><p>Calcium (Ca²⁺) and magnesium (Mg²⁺) are important for bone formation, muscle contraction and mass, and nerve function. Processes regulating Ca²⁺, Mg²⁺, parathyroid hormone (PTH), and vitamin D₃ are tightly coupled, ensuring proper bone metabolism and intestinal and renal absorption of Mg²⁺ and Ca²⁺. To better understand the synergy among these processes, mathematical modeling can be used in conjunction with experimental studies. Although several Ca²⁺ homeostasis models exist, computational models for studying Mg²⁺ homeostasis are much more limited. To fill this knowledge gap, we developed a model of Ca²⁺ and Mg²⁺ homeostasis in humans (more specifically, men), based on a previously published model in male rats. The model describes the exchanges of Ca²⁺, Mg²⁺, PTH, and calcitriol among five compartments: plasma, parathyroid gland, intestine, kidney, and bone. Given the increasing prevalence of dietary Mg²⁺ deficiency and its clinical importance as a risk factor for osteoporosis, we simulated severe dietary Mg²⁺ deficiency. Our model predicted a significant drop in PTH and calcitriol levels and an increase in bone resorption. In addition, we analyzed the systemic effects of diuretics, commonly used for the management of blood pressure and fluid balance. Although the pharmacological targets of diuretics typically directly mediate Na⁺ transport, they also indirectly alter renal Ca²⁺ and Mg²⁺ handling through changes in the transepithelial electrochemical gradient, thus affecting Ca²⁺ and Mg²⁺ balance. Model results suggest that acute administration of these three diuretics may not significantly perturb plasma concentrations of Ca²⁺, Mg²⁺, and the calciotropic hormones, whereas chronic administration can cause electrolyte and hormonal dyshomeostasis and affect bone mineral content.<b>NEW & NOTEWORTHY</b> The kidneys play an important role in maintaining the homeostasis of calcium and magnesium. Although diuretics directly affect the kidney's handling of sodium, they also indirectly affect renal calcium and magnesium reabsorption through changes in electrochemical gradients. How do diuretics affect whole body calcium and magnesium balance? To answer this question, we simulate the effect of acute and chronic administration of loop, thiazide, and K-sparing diuretics on renal transport and homeostasis of calcium and magnesium.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R272-R286"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526083","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 effects of 2 days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions.","authors":"Benjamin J Narang, Domen Tominec, Myrthe Stalmans, Grégoire P Millet, Chiel Poffé, Tadej Debevec","doi":"10.1152/ajpregu.00125.2025","DOIUrl":"10.1152/ajpregu.00125.2025","url":null,"abstract":"<p><p>High-altitude (HA) exposure induces an integrated physiological response to mitigate hypoxemia. Exogenous ketosis at simulated HA was previously shown to accentuate sympathetic activation and attenuate pulse oxygen saturation ([Formula: see text]) decreases through hyperventilation. The aim of this study was to extend these findings by investigating the effects of intermittent exogenous ketosis (IEK) across 2 days at terrestrial HA (3,375 m) on baroreflex sensitivity, heart rate variability, and hypoxic/hypercapnic ventilatory responses. Thirty-four healthy active adults completed neutral, hypoxic, and hypercapnic (0.03 [Formula: see text]) exposures, each comprising 6 min of seated rest, once at sea level (SL) and once after 2 days at HA. Across the 2 days, participants intermittently ingested either ketone monoester supplements (IEK) or placebo (PLA). During each exposure, blood pressure, ventilation, [Formula: see text], and end-tidal CO₂ pressure ([Formula: see text]) were continuously recorded, and arterialized capillary blood gas content was measured in the final 30 s. Baroreflex sensitivity and time-domain metrics of heart rate variability were reduced at HA (<i>P</i> = 0.006-0.043) but unaffected by group (<i>P</i> = 0.288-0.525). However, ventilation at HA under all three conditions was significantly higher in IEK compared with PLA (all <i>P</i> < 0.001). In hypoxia, this induced a higher [Formula: see text] (<i>P</i> = 0.038) and capillary O₂ pressure (<i>P</i> = 0.003). In hypercapnia, this induced a lower [Formula: see text] and capillary CO₂ tension (both <i>P</i> < 0.001). These results extend previous findings, suggesting that IEK enhances ventilation at terrestrial HA after 2 days of exposure, with this effect being independent from baroreflex sensitivity or heart rate variability changes.<b>NEW & NOTEWORTHY</b> This study demonstrates that 2 days of intermittent exogenous ketosis at 3,375 m terrestrial altitude does not alter baroreflex sensitivity or heart rate variability but significantly increases pulmonary ventilation under neutral, hypoxic, and hypercapnic conditions, improving oxygenation and lowering carbon dioxide retention. These findings suggest that ketone supplementation may enhance ventilatory acclimatization to high altitude via metabolic acidosis-driven respiratory stimulation, offering a nonpharmacological alternative to typical interventions used to support acclimatization.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R350-R362"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607163","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 antidipsogenic action of nesfatin-1 requires activation of a GLP-1 receptor.","authors":"Colleen R Bocke, Gina L C Yosten, Willis K Samson","doi":"10.1152/ajpregu.00087.2025","DOIUrl":"10.1152/ajpregu.00087.2025","url":null,"abstract":"<p><p>Nesfatin-1 is a potent inhibitor of food and water ingestion, and it has been reported that the anorexigenic and antidipsogenic actions of glucagon-like peptide-1 (GLP-1) require recruitment of nesfatin-1-producing neurons in the brain. Multiple neuropeptides appear to interact in reciprocal fashion to control ingestive behaviors. We demonstrate now that the antidipsogenic action of nesfatin-1 can be significantly reversed by pretreatment with the GLP-1 antagonist, exendin-3. Our prior work indicated that the antidipsogenic and anorexigenic actions of nesfatin could also be abrogated by blockage of melanocortin, corticotropin-releasing factor, and oxytocin signaling. We now propose a novel neuronal circuit activated by nesfatin-1, including those other peptide-expressing neurons.<b>NEW & NOTEWORTHY</b> Nesfatin-1 is a potent inhibitor of food intake and water drinking in rodents. We demonstrate here that the action of nesfatin-1 on water drinking depends on the recruitment of GLP-1 receptor-expressing neurons. These original observations further detail the neural circuitry regulating fluid ingestion.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R253-R257"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482846","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":"Impact of dopamine on baroreflex-mediated sympathetic arterial pressure regulation in rats: an open-loop analysis.","authors":"Nana Hiraki, Toru Kawada, Masafumi Fukumitsu, Takuya Nishikawa, Hiroki Matsushita, Yuki Yoshida, Kei Sato, Hidetaka Morita, Masahiro Otake, Kenta Ohba, Kazunori Uemura, Joe Alexander, Keita Saku","doi":"10.1152/ajpregu.00020.2025","DOIUrl":"10.1152/ajpregu.00020.2025","url":null,"abstract":"<p><p>Dopamine is commonly used to treat hemodynamic collapse, but its effect on baroreflex-mediated sympathetic arterial pressure (AP) regulation remains to be elucidated. We quantified the effects of dopamine on AP regulation using a baroreflex open-loop analysis by measuring sympathetic nerve activity (SNA) and AP in response to stepwise changes in carotid sinus pressure (CSP) before and during intravenous infusion of dopamine at 2, 10, and 20 µg·kg^-1·min^-1 in anesthetized rats (<i>n</i> = 8). We analyzed the CSP-SNA relationship (neural arc) and the SNA-AP relationship (peripheral arc) and constructed a baroreflex equilibrium diagram. The gain at the operating point was calculated from the product of the tangential slope of the neural arc and the slope of the peripheral arc. Compared with baseline, dopamine at 20 µg·kg^-1·min^-1 significantly reduced the maximum gain of the neural arc [from 1.898 ± 0.150 to 1.277 ± 0.205%/mmHg (<i>P</i> = 0.014)]. Compared with baseline, dopamine at 10 and 20 µg·kg^-1·min^-1 significantly reduced the slope of the peripheral arc [from 0.806 ± 0.079 to 0.645 ± 0.091 mmHg/% (<i>P</i> = 0.031) and 0.633 ± 0.100 mmHg/% (<i>P</i> = 0.020), respectively] and the operating point gain [from 0.800 ± 0.187 to 0.462 ± 0.153 mmHg/mmHg (<i>P</i> = 0.008) and 0.345 ± 0.122 mmHg/mmHg (<i>P</i> < 0.001)] while maintaining the operating point AP. In conclusion, dopamine at 10 and 20 µg·kg^-1·min^-1 maintained the operating point AP but significantly reduced the operating point gain for AP regulation, potentially increasing AP variability and instability.<b>NEW & NOTEWORTHY</b> Dopamine impaired the arterial pressure (AP) buffering effect mediated by the arterial baroreflex while maintaining AP in anesthetized normal rats. This previously unrecognized effect of dopamine may partially explain why the use of dopamine did not yield favorable outcomes in clinical trials, particularly in patients with shock in whom acute hemodynamic fluctuations can be life-threatening.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R329-R339"},"PeriodicalIF":2.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599129","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":"Modeling COPD in <i>Drosophila melanogaster</i> by cigarette smoke inhalation: functional changes and alterations in the expression of COPD-relevant orthologous genes.","authors":"Periklis Marnas, Stefan Lüpold, Lydia Giannakou, Athanasios-Stefanos Giannopoulos, Chrissi Hatzoglou, Konstantinos I Gourgoulianis, Sotirios G Zarogiannis, Erasmia Rouka","doi":"10.1152/ajpregu.00056.2025","DOIUrl":"10.1152/ajpregu.00056.2025","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) ranks as the fourth leading cause of mortality worldwide. Long-term exposure to airway irritants such as smoking and air pollution is the main risk factor for developing the disease. Expanding on previous in silico findings on COPD-relevant orthologous genes between humans and <i>Drosophila melanogaster</i>, we experimentally investigated the contribution of cigarette smoke (CS) inhalation exposure to the induction of COPD-related physiological and transcriptomic modifications. Adult flies 2-4 days old were exposed to CS via inhalation for 20 min over five consecutive days. The metabolic rate, locomotor activity, body mass, total body length, and the expression of COPD-specific genes were measured and compared between the exposed and unexposed groups. CS inhalation exposure significantly increased the metabolic rate and decreased the locomotor activity, body weight, and total body length. Transcriptomic changes were more profound in females, indicating sex-specific differences in CS-induced molecular responses. Functional enrichment analyses of the differentially expressed COPD-relevant genes in females pointed toward ABC transporters, miR-313 microRNA, abnormal developmental rate, DNA repair, and cell differentiation. Our results indicate that <i>D. melanogaster</i> is a powerful model organism for studying the pathophysiological changes associated with COPD. Future work should focus on establishing tracheolar-related changes that would reflect histopathological perturbations similar to COPD patients' airways.<b>NEW & NOTEWORTHY</b> Inhalation exposure of adult <i>D. melanogaster</i> to cigarette smoke induced changes in physiological parameters and the expression of COPD-associated orthologous genes. Transcriptomic responses were more profound in females, indicating sex-specific responses to inhaled toxicants. Furthermore, enrichment analyses of the differentially expressed genes in females pointed to biomolecules associated with response to nicotine and detoxification. <i>D. melanogaster</i> thus provides a powerful model system to test the efficacy of new potential drugs for COPD treatment.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R13-R19"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109385","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}