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

{"title":"Breaking the cycle: examining the role of endogenous and exogenous sex hormones on arterial stiffening in premenopausal women with PTSD.","authors":"Emily A Larson, Kerrie L Moreau","doi":"10.1152/ajpregu.00051.2025","DOIUrl":"10.1152/ajpregu.00051.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R506-R508"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656122","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":"Exercise pressor reflex function is augmented in rats with chronic kidney disease.","authors":"Han-Kyul Kim, Juan A Estrada, Ayumi Fukazawa, Amane Hori, Gary A Iwamoto, Scott A Smith, Masaki Mizuno, Wanpen Vongpatanasin","doi":"10.1152/ajpregu.00234.2024","DOIUrl":"10.1152/ajpregu.00234.2024","url":null,"abstract":"<p><p>Cardiovascular responses to exercise are exaggerated in patients with chronic kidney disease (CKD). Enhanced sympathetic activation is thought to play a role with the exercise pressor reflex (EPR), a reflex originating in contracting muscle, modulating this response. Previous studies suggest an overactive EPR in patients with CKD as indicated by muscle sympathetic overactivation during static handgrip exercise. However, the role of the EPR could not be fully elucidated due to experimental constraints inherent to humans. The purpose of this study was to specifically test EPR function in a CKD animal model. Male Sprague-Dawley rats were assigned to a diet containing 0.25% adenine to induce CKD or a control diet. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to activation of the EPR, including its functional components, the mechanoreflex and metaboreflex, were assessed in decerebrate, unanesthetized animals after feeding 10-14 wk. Plasma creatinine was significantly higher in CKD rats compared with controls (1.80 ± 0.78 vs. 0.34 ± 0.02 mg·dL^-1, <i>P</i> = 0.017). MAP and RSNA responses to muscle contraction (i.e., EPR activation) were potentiated in CKD rats compared with controls (Δ = 36 ± 19 vs. 17 ± 8 mmHg, <i>P</i> = 0.014 and Δ = 159 ± 62 vs. 64 ± 54%, <i>P</i> = 0.004, respectively). Similarly, the pressor and sympathetic responses to passive muscle stretch (i.e., mechanoreflex stimulation) were significantly higher in CKD than in control animals. Intra-arterial capsaicin administration (i.e., metaboreflex activation) induced an augmented pressor response in CKD rats, compared with controls. Our findings suggest that the EPR, stimulated by the mechanoreflex and metaboreflex, is exaggerated in CKD.<b>NEW & NOTEWORTHY</b> The current investigation identifies that activation of the exercise pressor reflex (EPR) by hindlimb muscle contraction generates exaggerated pressor responses in a chronic kidney disease (CKD) animal model. This hypertensive response is accompanied by sympathetic overactivation during EPR stimulation, with both the muscle mechanoreflex activated by passive muscle stretch and the muscle metaboreflex stimulated by intra-arterial capsaicin administration, contributing to the heightened pressor effect. These findings suggest augmented EPR, mechanoreflex, and metaboreflex function in CKD.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R460-R469"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490567","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":"A new link between low testosterone and cardiovascular disease risk.","authors":"Grace S Maurer, Anna E Stanhewicz","doi":"10.1152/ajpregu.00043.2025","DOIUrl":"10.1152/ajpregu.00043.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R492-R493"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603535","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":"IL-6 induces mitochondrial ROS production and blunts NO bioavailability in human aortic endothelial cells.","authors":"Prema Velusamy, David J Buckley, Jody L Greaney, Adam J Case, Paul J Fadel, Daniel W Trott","doi":"10.1152/ajpregu.00289.2024","DOIUrl":"10.1152/ajpregu.00289.2024","url":null,"abstract":"<p><p>Chronic inflammation is a major contributor to the development of endothelial dysfunction. Circulating concentrations of the proinflammatory cytokine interleukin-6 (IL-6) have been shown to predict cardiovascular disease risk and are associated with the development of vascular dysfunction. However, the mechanisms that underlie inflammation-induced endothelial dysfunction are not fully understood. Vascular endothelial dysfunction is characterized by blunted nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS), with mitochondrial ROS suggested to play a primary role. Therefore, we tested the hypothesis that IL-6 induces mitochondrial ROS production and blunts NO bioavailability in endothelial cells. To study the effect of IL-6, we treated the human aortic endothelial cells (HAECs) with IL-6, MitoTEMPOL (MT; a mitochondria-targeted antioxidant), and/or a nitric oxide synthase (NOS) inhibitor (l-NAME) with and without ACh stimulation. Results are expressed as means ± SD (<i>n</i> = 4 replicates), one-way ANOVA, and Bonferroni's post hoc tests were performed. IL-6 treatment resulted in greater mitochondrial ROS (IL-6: 2.94 ± 0.93 a.u.) when compared with the untreated cells (Control: 1 ± 0; <i>P</i> = 0.0021) and also blunted NO bioavailability at baseline (Control: 1 ± 0; IL-6: 0.57 ± 0.08 a.u. <i>P</i> = 0.0008) and with acetylcholine stimulation (Control Ach: 1.27 ± 0.09; IL-6 Ach: 0.60 ± 0.13 a.u. <i>P</i> < 0.0001). Scavenging mitochondrial ROS with MT restored NO bioavailability in the IL-6-treated cells (IL-6: 0.57 ± 0.08; IL-6 MT: 1.16 ± 0.20 a.u. <i>P</i> < 0.0001). These findings indicate that IL-6 has a direct effect on mitochondrial ROS in human aortic endothelial cells, which leads to reduced nitric oxide bioavailability.<b>NEW & NOTEWORTHY</b> In this study, we provide evidence that IL-6 induces mitochondrial ROS production, which impairs nitric oxide bioavailability in human aortic endothelial cells. This finding adds an important perspective to the existing literature on the mechanism by which IL-6 contributes to endothelial dysfunction.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R509-R514"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699400","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":"Heat-producing thermoeffector plasticity in response to prolonged iterative exposure to a high-heat loss environment: no indication of thermoregulatory fatigue.","authors":"Maaike I Moes, Antonis Elia, Ola Eiken, Michail E Keramidas","doi":"10.1152/ajpregu.00310.2024","DOIUrl":"10.1152/ajpregu.00310.2024","url":null,"abstract":"<p><p>Previous studies have suggested that, during prolonged cold exposure, shivering thermogenesis may gradually be attenuated, supposedly reflecting a state of central fatigue (aka 'thermoregulatory fatigue') provoked by extended shivering activity, that precipitates hypothermia. The purpose of this study was to revisit the validity of this notion. Twelve noncold-acclimatized men participated in three ∼10-h sessions, during which they performed repeatedly three 120-min cold-water immersions. To induce discrete amounts of heat-producing thermoeffector output, presumptively leading to distinct levels of fatigue during each session, subjects were submersed, within each session, in either severely (15°C), moderately (20°C), or slightly (28°C) cold water. The cold-induced elevation in thermogenic rate was similar across the three repeated immersions performed within the 15°C (∼130 W·m²) and 20°C (∼100 W·m²) sessions (<i>P</i> ≥ 0.43). In the 28°C-session, the metabolic heat production was augmented by ∼7% in the second and third immersions compared with the first immersion (<i>P</i> = 0.01). No intrasession differences were noted with regards to the body-core cooling rate, the cold-induced drop in skin temperature and forearm cutaneous vascular conductance, or the stress-hormone (salivary α-amylase and cortisol concentrations) and thermoperceptual responses (<i>P</i> > 0.05). The present findings, therefore, demonstrate that the ability to generate heat remains intact during prolonged iterative exposure to a high-heat loss environment in a single day, regardless of the severity of cold stressor. The intermittent application of slight cold stress (i.e., 28°C water) appears to mediate metabolic sensitization, reflecting either the circadian rhythmicity of heat-producing thermoeffector activity, or perhaps the rapid induction of metabolic adaptation.<b>NEW & NOTEWORTHY</b> The study evaluated whether centrally mediated thermoregulatory fatigue is provoked by prolonged exposure to uncompensable cold. Regardless of the severity of cold stressor, the ability to produce endogenous heat remains intact during prolonged iterative exposure to a high-heat loss environment.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R433-R446"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466665","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":"Immunohistochemistry as a technique in the studies on the neuroendocrine control of hydromineral balance: the legacy of José Antunes-Rodrigues.","authors":"Cristiane Mota Leite, Silvia Graciela Ruginsk, Laura Vivas, Andrea Godino, Ernane Torres Uchôa","doi":"10.1152/ajpregu.00247.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00247.2024","url":null,"abstract":"<p><p>Several forebrain and brainstem neurochemical circuitries interact with peripheral, neural, and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Over the past decades, much progress has been made in understanding the complex mechanisms underlying the neuroendocrine control of hydromineral homeostasis. Classical experiments performed by Dr. Antunes-Rodrigues in the early 1960s, such as lesions of hypothalamic and extra-hypothalamic areas and drug microinfusions, associated with behavioral analysis and electrolytes/hormones measurements, were crucial to elucidate several aspects of the regulation of hydromineral balance. Fifty years after this pioneering research, the use of immunohistochemistry shifted methodological efforts to the central nervous system, in an attempt to elucidate how neurons (and lately, also glial cells) receive and interpret sensory signals originating from the periphery. This report focuses on the main findings obtained by Dr. Antunes-Rodrigues and colleagues using immunohistochemistry as an important tool in the first two decades of this century to elucidate the brain specific neurochemical circuits underlying functional mechanisms by which osmotic and volume challenges could impact hormonal and behavioral responses.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655559","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 effect of an exercise- and passive-induced heat stress on autophagy in young and older males.","authors":"James J McCormick, Kelli E King, Nicholas Goulet, Andres E Carrillo, Naoto Fujii, Tatsuro Amano, Pierre Boulay, Glen P Kenny","doi":"10.1152/ajpregu.00232.2024","DOIUrl":"10.1152/ajpregu.00232.2024","url":null,"abstract":"<p><p>Although activation of autophagy is vital for cellular survival during exposure to ambient heat and exercise, it remains unclear if autophagic activity differs between these heat stress conditions and if aging mediates this response. Young [<i>n</i> = 10, mean (SD): 22 (2) yr] and older males [<i>n</i> = 10, 70 (5) yr] performed 30 min of semi-recumbent cycling (70% maximal oxygen uptake). On a separate day, participants were immersed in warm water for 30 min, with the water temperature adjusted to induce the same increase in core temperature (rectal) as the prior exercise bout. Proteins associated with autophagy, inflammation, apoptosis, and the heat shock response (HSR) were assessed in peripheral blood mononuclear cells via Western blot before and after each exposure and during a 6-h seated recovery in a temperate environment (∼22°C). No differences in core temperature occurred at end-exposure to exercise or passive heating in either group (both, <i>P</i> ≥ 0.999). Older adults exhibited greater autophagic regulation (significant LC3-II accumulation) to exercise when compared with passive heating at all time points (all, <i>P</i> ≤ 0.022). However, passive heating alone may have impaired autophagy (elevated p62; <i>P</i> = 0.044). Pro-inflammatory IL-6 was elevated during both conditions (<i>P</i> < 0.001) in older adults. Conversely, greater autophagic initiation (i.e., beclin-2) occurred in young adults at end-exercise and 3-h recovery when compared with passive heating (both, <i>P</i> ≤ 0.024). The HSR and apoptotic responses were similar between conditions in both groups. Although brief exercise stimulates autophagy, exposure to ambient heat stress of an equivalent heat load may underlie autophagic dysregulation in older adults.<b>NEW & NOTEWORTHY</b> We show that a short-duration (30-min) bout of vigorous-intensity exercise stimulates autophagy in young and older males when performed in a temperate environment. However, when exposed to an equivalent heat load as achieved during the prior exercise bout to elicit the same relative increase in core temperature via warm-water immersion, autophagic dysregulation occurs in older but not younger males.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R289-R299"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188168","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":"Submandibular gland removal decreases avoidance of bitter taste in mice.","authors":"Masataka Narukawa, Yukino Matsuhara, Remi Umano, Momo Murata, Ippei Watari, Takashi Ono, Takumi Misaka","doi":"10.1152/ajpregu.00290.2024","DOIUrl":"10.1152/ajpregu.00290.2024","url":null,"abstract":"<p><p>Saliva plays a crucial role in digestion, including taste perception, food breakdown, chewing, swallowing, and bolus formation. Saliva is mainly produced by three pairs of major glands: parotid, submandibular, and sublingual glands. To evaluate the effect of each salivary gland on taste preference, we conducted a 48-h two-bottle preference test using mouse models in which the parotid glands (PGs), submandibular glands (SMGs), or sublingual glands (SLGs) were surgically removed. The taste preferences for the five basic tastes of the PG- and SLG-removed mice were similar to those of the control mice. However, in SMG-removed mice, the avoidance of bitter compounds was significantly decreased. These findings indicate that the SMG plays an important role in bitter taste perception among the three major salivary glands. To investigate the reasons for this preference change, we examined the impact of salivary gland removal on the expression of taste-related molecules in the taste buds. No apparent changes were observed in the expression of these molecules after salivary gland removal. When comparing the protein concentration and composition of saliva between the control and salivary gland removal groups, we found that, although the protein concentration did not change significantly, its composition was substantially altered by SMG removal. These results suggest that changes in protein composition in saliva may be one of the factors responsible for the altered bitter preferences observed in the SMG-removed mice.<b>NEW & NOTEWORTHY</b> Using mouse models with surgically removed parotid glands (PGs), submandibular glands (SMGs), or sublingual glands (SLGs), we examined taste preferences. PG- and SLG-removed mice showed no significant changes in preference, but SMG removal notably reduced the avoidance of bitter compounds. Although the salivary protein concentration remained unchanged, its composition was altered by SMG removal, suggesting that these changes may underlie the modified perception of bitter taste.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R300-R305"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363475","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":"Oral contraceptive pill phase alters mechanisms contributing to cutaneous microvascular function in response to local heating.","authors":"Casey G Turner, Anna E Stanhewicz, Karen E Nielsen, Jeffrey S Otis, Rafaela G Feresin, Brett J Wong","doi":"10.1152/ajpregu.00159.2024","DOIUrl":"10.1152/ajpregu.00159.2024","url":null,"abstract":"<p><p>The purpose of this study was to investigate the effect of oral contraceptive pill (OCP) phase on in vivo microvascular endothelium-dependent vasodilation and contributions of nitric oxide (NO), cyclooxygenase (COX), and endothelial-derived hyperpolarizing factors (EDHFs). Participants completed two experimental visits in random order, during the <i>1</i>) low and <i>2</i>) high hormone phase of the OCP cycle. Endothelium-dependent dilation was assessed in the cutaneous microvasculature via local heating at four intradermal microdialysis sites treated with: <i>1</i>) lactated Ringer's (control), <i>2</i>) 10 mM ketorolac (Keto, COX inhibitor), <i>3</i>) 50 mM tetraethylammonium (TEA, calcium-activated potassium channel inhibitor), and <i>4</i>) 10 mM ketorolac + 50 mM TEA (Keto + TEA). Perfusion of 20 mM <i>N</i>^ω-nitro-l-arginine methyl ester (l-NAME) at each site was used to quantify the l-NAME-sensitive component of dilation, suggesting NO contribution. There was no effect of OCP phase on endothelium-dependent dilation (<i>P</i> = 0.75) or the l-NAME-sensitive component of the response (<i>P</i> = 0.09, <i>d</i> = 0.7) at control sites. Inhibition of COX increased baseline blood flow regardless of OCP phase (all <i>P</i> < 0.01). Control and Keto sites elicited greater endothelium-dependent dilation than TEA and Keto + TEA sites in both phases (all <i>P</i> < 0.0001). During the low hormone phase, the l-NAME-sensitive component was greater at control compared with TEA sites (<i>P</i> < 0.01). During the high hormone phase, the l-NAME-sensitive component was greater at Keto compared with TEA sites (<i>P</i> < 0.01). Within-participant differences between control and Keto sites support a phase-dependent restraint of NO activity via COX pathways (<i>P</i> = 0.01). These findings demonstrate that the OCP phase affects underlying mechanistic pathways contributing to cutaneous microvascular endothelial function.<b>NEW & NOTEWORTHY</b> This study investigates the effect of OCP phase on in vivo microvascular endothelium-dependent vasodilation and explores underlying mechanisms. Present findings suggest OCP phase does not affect overall microvascular endothelium-dependent dilation but does affect the underlying mechanisms. In women using OCP, there is a robust reliance on EDHF pathways and the COX pathway moderates basal microvascular blood flow and demonstrates a phase-dependent restraint of the NO pathway.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R374-R385"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405173","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":"Sex differences in the central and peripheral omega 3 oxylipin response to acute systemic inflammation.","authors":"Julia C Kelliher, Ivana Maric, Christopher G Engeland, Gregory C Shearer, Karolina P Skibicka","doi":"10.1152/ajpregu.00242.2024","DOIUrl":"10.1152/ajpregu.00242.2024","url":null,"abstract":"<p><p>High-density lipoprotein (HDL) oxylipins regulate inflammation, and acute systemic inflammation can precipitate cognitive impairment. Females have more HDL and stronger immune responses than males, yet higher dementia risk. Little is known about sex differences in oxylipin responses to inflammatory stimuli and potential crosstalk between acute systemic inflammation and central oxylipin signaling in either sex. In this targeted lipidomics study, we used liquid chromatography with tandem mass spectrometry (LC/MS/MS) to characterize oxylipin profiles in plasma HDL and cerebrospinal fluid (CSF) of male and female rats following an intraperitoneal interleukin-1β (IL-1β)-induced inflammatory challenge to determine whether and how peripheral and central oxylipins respond to acute systemic inflammation in both sexes. We hypothesized that females mount a greater oxylipin response to IL-1β than males and that acute activation of peripheral inflammatory pathways changes central oxylipin concentrations. We found that IL-1β altered the abundance of omega (ω)6 and ω3 oxylipins in plasma HDL and CSF of both sexes. However, IL-1β reduced global concentrations of peripheral and central oxylipins in plasma HDL and CSF, respectively, in female rats only. Reduced oxylipin concentrations in IL-1β-treated females were driven by a loss of anti-inflammatory ω3 eicosapentaenoic acid (EPA)-derived dihydroxyeicosatetraenoic acids (DiHETEs) in plasma HDL and CSF. Interestingly, plasma HDL and CSF concentrations of EPA-derived DiHETEs were only correlated in IL-1β-treated rats, suggesting increased periphery-brain crosstalk during acute systemic inflammation. Overall, the sexually dimorphic responses of peripheral and central oxylipins to acute systemic inflammation provide molecular insight into sex differences in both innate immunity and neuroinflammatory responses.<b>NEW & NOTEWORTHY</b> This study examines previously unexplored sex differences in oxylipin signaling cascade activation in the central nervous system and periphery during the acute phase response. This is the first study to assess and correlate oxylipins in plasma HDL and CSF in males and females following an acute systemic inflammatory challenge. This work showing reduced concentrations of anti-inflammatory ω3 EPA-derived DiHETEs in acutely inflamed females provides molecular insight into sex differences in immunity and inflammation-induced neurological changes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R341-R351"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881101","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}