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Background: During hypoxic exercise, oxygen transport becomes increasingly challenged as oxygen availability decreases. As the inspired oxygen fraction (FiO 2 ) decreases, peripheral oxygen saturation (SpO 2 ) gradually declines, then drops rapidly upon reaching the steepest point of the sigmoidal shaped, oxyhemoglobin dissociation curve. This reduction in FiO 2 creates a distinct SpO 2 “breakpoint,” which likely represents the threshold at which compensatory mechanisms, such as increases in ventilation and cardiac output, can no longer maintain arterial oxygenation. Several physiological factors may modulate this breakpoint, including hemoglobin concentration, blood volume, and ventilatory capacity. This study aimed to determine the SpO 2 breakpoint during steady-state, submaximal, hypoxic exercise and examine whether factors like sex, age, and fitness level influence the SpO 2 breakpoint. We hypothesized that SpO 2 breakpoints would differ by sex, age, and fitness level, with earlier breakpoints visible in females, older adults, and those with higher aerobic fitness. Methods: Twenty-six physically active adults (15M: age 35±9 yrs, [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 38±10 yrs, [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) participated in a two-day study. Day one: participants performed a treadmill [Formula: see text]O 2 max test. Day two: participants walked at a steady state of ~50% of their [Formula: see text]O 2 max, for 40 minutes, while FiO 2 was progressively reduced every 5 minutes in a stepwise fashion (0.25, 0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). The test was terminated when SpO 2 dropped below 70%. SpO 2 was measured continuously using a clinical-grade oximeter. Analysis was performed in RStudio by first determining each participant’s individual SpO 2 vs time breakpoint. Male and Female breakpoints were compared to assess sex-based differences. To evaluate whether SpO 2 breakpoint timing differed by age or fitness level, participants were then divided into tertiles for each variable. Age tertiles were derived from the sample distribution of chronological age, and fitness tertiles were defined using [Formula: see text]O 2 max (L/min). Mean breakpoint times were compared between the highest and lowest tertiles for both age and fitness. Mean SpO 2 breakpoints were compared between groups using independent sample t-tests. Significance was set to p< 0.05. Results: The overall mean breakpoint occurred at an SpO 2 of 90.7±2.8% during the 0.17 FiO 2 stage. No significant sex differences were observed in breakpoint SpO 2 and timing (M: SpO 2 = 90.7±2.7%, time = 18.6 min; F: SpO 2 = 90.7±3.0%, time = 17.7 min; p = 0.961). Age did not significantly influence breakpoint (younger tertile [21-30 yrs] SpO 2 = 91.0±2.4%, time = 18.4 min; older tertile [41-60 yrs] SpO 2 = 91.1±2.4%, time = 17.2 min, p = 0.953). Additionally, fitness level showed no significant difference on breakpoint (low fitness [1.91-3.01 L/min]: SpO 2 = 90.3±3.1%, time = 17.8 min; high fitness [4.38-5.25 L/min]: SpO 2 = 90.4±2.9%, time = 19.2 min; p = 0.992). Conclusion: During a hypoxic, steady state walking exercise, at ~50% [Formula: see text]O 2 max, we observed no difference in the peripheral oxygen saturation breakpoint, across sex, age, and fitness level. This may suggest that moderate exercise in hypoxia does not sufficiently challenge the cardiopulmonary system for individual variations in oxygen transport to influence the breakpoint. These findings imply that the SpO 2 breakpoint, during hypoxic exercise, may represent a physiological marker of the upper limit for maintaining oxygen saturation in healthy adults. Applying this protocol to identify SpO 2 breakpoints may offer insights for improving pharmacological interventions and our understanding of clinical populations with impaired oxygen transport. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Neuromotor control of sighs consists of two phases: Phase I, which resembles a preceding eupneic breath, and Phase II, an extra inspiration superimposed on Phase I. The diaphragm muscle (DIAm)—the primary inspiratory muscle in mammals—is activated during multiple behaviors, including sighs, and its activity can be quantified using electromyography (EMG). Although the biphasic structure of sighs has been described using airflow and pressure signals, how these phases are represented in DIAm EMG activity—and the underlying dynamics of DIAm motor unit (MU) recruitment—remains unclear. Previously we described that eupnea consists of a period of MU recruitment followed by a period of sustained MU activity before derecruitment. We hypothesize that during sighs Phase I follows a similar trajectory of MU recruitment as eupnea while Phase II reflects superimposed additional MU recruitment. DIAm EMG was recorded using fine wire electrodes in awake Sprague-Dawley rats (n=6) of both sexes. To determine the period of DIAm MU recruitment during both Phase I and Phase II, a stationarity analysis was performed. The stationarity analysis uses a reverse arrangement test applied to sequential, non-overlapping 10-ms bins across a longer analysis window. Because DIAm MU discharge rates rarely exceed 100 Hz, it is unlikely that a single MU fires more than once within each 10-ms window; thus, non-stationarity reflects MU recruitment rather than changes in discharge rate. An average of 17 ± 4 sighs per animal were identified (range: 10-20), with a frequency of 2.8 ± 0.1 min-1. Sighs had a burst duration of 1300 ± 405 ms, much longer than the burst duration of eupneic breaths (~598 ± 111 ms). During sighs there were two distinct periods of MU recruitment reflected by non-stationarity of the EMG signal. The MU recruitment duration of Phase I was significantly shorter than Phase II (100 ± 28 ms vs. 179 ± 53 ms, p = 0.041). The onset-to-peak duration during sighs averaged 489 ± 135 ms, with the duration of Phase I lasting longer than Phase II (298 ± 119 ms vs 179 ± 56 ms). It is important to note that Phase II is characterized by rapid, continuous recruitment throughout its duration. In contrast, Phase I had a longer overall duration, although the period of MU recruitment was relatively brief—similar to eupneic breathing. Using EMG stationarity in awake animals allowed us to characterize these underlying MU patterns without altering ventilation or disrupting the intact of the respiratory system. These results indicate that sighs reflect a distinct pattern generator superimposed on that generating eupneic breathing. It remains unclear whether sighs are triggered (e.g., reflexes) or spontaneously generated. Funding: NIH NHLBI 5R01HL146114 and NIA 5R01AG044615 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Aged heterozygous endothelial nitric oxide synthase knockout mice (eNOS+/−) represent an important model of spontaneous cerebral small vessel disease. However, the role of endothelium in vasomotor function of cerebral arteries of aged eNOS+/− mice has not been characterized. In the process of generating endothelial specific β-site amyloid precursor protein cleaving enzyme-1 (BACE1)/eNOS+/− knockout mice, we performed control studies in 18 months old male eNOS+/− mice and their wild-type littermates generated on floxed C57BL/6-Bace1tm1.1mrl background. Vasomotor function of isolated basilar arteries was studied in vitro under pressurized conditions using a video dimensions analyzer. Contractions to acetylcholine were observed in aged eNOS+/− mice (19±13%), while acetylcholine caused endothelium-dependent relaxations in age-matched wild-type littermates (-17±7%, P< 0.05; n=9 per group). In contrast, endothelium-independent relaxations to NO-donor diethylamine-NONOate were unaltered in both wild-type littermates (-83±10%) and eNOS+/− mice (-90±4%; n=6 per group; P >0.05). Furthermore, contractions to U46619 were significantly augmented in eNOS+/− mice (63±3%; P< 0.05 vs. wild-type: 47±4%; n=6). Morphological analysis revealed that lumen diameter of basilar arteries was not different between wild-type (169±4 µm) and eNOS+/− mice (165±4 µm; P >0.05; n=9). Furthermore, blood glucose levels were comparable between wild-type (185±7 mg/dL) and eNOS+/− mice (183±12 mg/dL; P >0.05; n=10). Measurement of lipid profile showed that plasma cholesterol, HDL as well as triglyceride levels were unchanged in eNOS+/− mice (P >0.05 vs. wild-type; n=10). Interestingly, mRNA expression of BACE1 is significantly increased in cerebral arteries of aged eNOS+/− mice (0.0295±0.0009) as compared to wild-type littermates (0.0243±0.0017; P< 0.05; n=5 per group). Our results demonstrate that heterozygous eNOS deficiency exacerbates endothelial dysfunction in aged eNOS+/− mice and is accompanied by the imbalance between vasodilation and vasoconstriction of cerebral arteries. Endothelial dysfunction in aged eNOS+/− mice appears to be independent of alterations in systemic metabolic parameters. Notably, partial deficiency of eNOS increases expression of BACE1, an enzyme responsible for production of amyloid-β peptides. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

We previously showed that the Drosophila Malpighian tubule (MT) can model the formation of calcium oxalate (CaOx) kidney stones. Two epithelial cell types, stellate cells (SC) and principal cells (PC) comprise MTs, with each transporting different solutes from the hemolymph to MT lumen. Prestin, Neat and Ndae1 contribute to transepithelial ox2-, HCO 3 - transport and fluid secretion. Neat (2HCO 3 - /ox2- exchange) and NDAE1 (Na + ,2HCO 3 - /Cl - exchange) functionally combine to takeup hemolymph ox2-, can also facilitate HCO 3 - uptake. Prestin then secretes ox2- via Cl - / ox2-exchange to create luminal MT CaOx crystals, but it can also exchange Cl - /HCO 3 - . This study examines transepithelial ion secretion by Prestin (Slc26a6, apical), Neat (Slc26a1-like, basal) and Ndae1 (Slc4a8-like, basal). We use a functionally similar, simple genetic model (Drosophila Malpighian tubules, MT) to measure renal CaOx crystallization (NaOx feeding), membrane transport (pHi, fluorescent pH sensors) and fluid secretion (Ramsey assay) to: (1) compare cell-specific gene knockdown (KD) vs gene knockout, (2) quantify CaOx crystallization and intracellular pH (pHi) regulation by CO 2 /HCO 3 - , and (3) humanize these transporters by replacing them with human homologs. We hypothesize that humanizing individual transporters will restore MT physiology. Candidate transporter genes are tested for transepithelial ox2-and HCO 3 - secretion with gene-specific knockdown or knockout, using CRIMIC (CRISPR-Mediated Integration Cassette) alleles, in MTs due to comparable function to mammalian nephrons. Neat and NDAE1 work together to take-up hemolymph ox2- or HCO 3 - then Prestin secretes ox2- or HCO 3 - into the MT lumen. Prestin, Neat or NDAE1 knockdowns in principal cells decrease CaOx crystals. NDAE1 but not Neat knockdown in SC increases CaOx crystals like AQP (Drip, Prip)-knockdowns while either KD enhance HCO 3 - transport. Ndae1-SC-KD reduces fluid secretion like AQP-KD. Each CRIMIC allele must be physiologically compared to PC/SC-KDs because Ndae1-KO but not Neat-KO mirrors PC rather than SC function. Ndae1-SC-KD shows that HCO 3 - and Cl - secretion cause fluid secretion. Human homolog replacements are on-going. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Brain-derived neurotrophic factor (BDNF) signals through its high-affinity full length tropomyosin receptor kinase-B (TrkB.FL). One key downstream target of BDNF/TrkB.FL signaling is phosphorylation of the transcription factor cyclic AMP response element-binding (CREB) protein at serine 133 (pCREBS133). We hypothesized that a positive feedback loop exists in the spinal cord in which BDNF/TrkB.FL induces pCREBS133 which then transcriptionally targets pro-BDNF expression. To test this hypothesis, we employed a loss of function approach using a novel chemogenetic rat model (TrkBF616A) with a knock-in allele sensitive to the selective kinase inhibitor 1NMPP1 to inhibit TrkB.FL kinase activity. In female and male TrkBF616A rats, we then examined the effects of 1NMPP1 (orally through drinking water) induced TrkB.FL kinase inhibition on BDNF levels in the cervical (CSC) and lumbar (LSC) spinal cord. The spinal cord was collected at two time points at 0700 and 010 reflecting the trough and peak timepoints of endogenous BDNF expression. BDNF levels were quantified using ELISA. We found in the CSC, BDNF levels did not vary across timepoints in either 1NMPP1 or vehicle treated groups. However, 1NMPP1-induced TrkB.FL inhibition significantly reduced BDNF levels at both timepoints (P=0.004). This reduction suggests that cervical circuits rely on continuous CREB-dependent support of BDNF expression and that inhibiting TrkB.FL disrupts this loop throughout the day. In the LSC, control rats displayed time of day-dependent variations in BDNF with lower levels at 0700 compared to 0100 (P=0.02). In contrast, 1NMPP1-induced inhibition of TrkB.FL reduced BDNF levels at 0100—when BDNF normally peaks in the LSC (P=0.01). This nighttime specific deficit supports the idea that activity-driven pCREBS133 activation is necessary to elevate BDNF during the active phase and that blocking TrkB.FL signaling disrupts this pCREBS133-mediated positive feedback. Overall, these results support a positive feedback that is region- and time-specific and involves BDNF/TrkB.FL signaling inducing pCREBS133 phosphorylation which then targets pro-BDNF expression in the spinal cord. Supported by NIH grants HL146114 and AG44615. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Obesity is a complex metabolic disease that is the leading risk factor for cardiovascular disease. In obesity, adipose arteries exhibit robust endothelial dysfunction (ED). A major hallmark of ED is loss in flow induced vasodilation (FIV). Kir2.1 is an inwardly rectifying K+ channel that contributes to FIV through the downstream production of nitric oxide, a potent vasodilator. Work from our group demonstrated that in addition to loss in FIV, endothelial cells (ECs) isolated from obese mice exhibited blunted Kir2.1 currents. Plasma long chain fatty acids (LCFAs) are well established to be elevated in obesity and have been separately shown to inhibit Kir2.1 channels. CD36 is the major fatty acid translocase responsible for the uptake of LCFAs and we therefore aimed to determine if CD36 was contributing to this loss in Kir2.1 function. We previously showed that global CD36 ablation restores endothelium-dependent dilations to flow. These findings prompted us to explore the role of EC CD36 in negatively regulating Kir2.1 function. We performed patch clamp electrophysiology experiments on freshly isolated ECs from the Tie2eCreCD36fl/fl model and determined that EC CD36 ablation restores Kir2.1 currents in obesity. To further explore the established relationship between Kir2.1 and FIV, we performed ex vivo pressure myography experiments to evaluate endothelial dependent dilations to flow. EC CD36 ablation restored responses to flow in arteries from obese mice, an effect that could be blunted by inhibiting Kir2.1 suggesting that CD36 ablation in endothelium rescues the Kir2.1 contribution to FIV. To determine if obesity alters the expression of endothelial CD36, arteries from mice and humans undergoing bariatric surgery were isolated and en face preparations were stained to locate the EC layer and assess CD36 expression. Confocal imaging of en face arteries coupled with flow cytometry on isolated endothelial cells revealed that obesity did not alter the expression of CD36 in endothelium of mesenteric arteries relative to controls in WT mice or humans. As expression did not change, we next probed functionality of CD36 in obese vs. control in mice and humans. Arteries were exposed to a fluorescent fatty acid, BODIPY C-16, at various time points followed by en face preparations and confocal microscopy. As expected, obese vessels exhibited elevated amounts of fatty acid uptake (FAU) at all time points relative to control in mice and humans, suggesting an increase in CD36. To further confirm this change in function, we repeated FAU experiments in the Tie2eCreCD36fl/fl model and found that EC CD36 ablation attenuated FAU in obese vessels compared to both their lean and genotype controls. Taken together, this work suggests that an increase in CD36 function drives impairment of Kir2.1. This work establishes a CD36/Kir2.1 axis worthy of further exploration including understanding how CD36 and LCFAs are impairing Kir2.1 upstream. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Neuromotor control of diaphragm muscle (DIAm) involves size-dependent recruitment of phrenic motor neurons (PhMNs). To accomplish breathing, only smaller PhMNs innervating slow (type S) and fast, fatigue resistant (type FR) DIAm motor units are recruited. Thus, smaller PhMNs and type S and FR DIAm motor units are very active in sustaining ventilation throughout life. Larger PhMNs innervating more fatigable fast (type FF) motor units are very infrequently recruited for higher force, expulsive behaviors. Previously, we reported that smaller PhMNs have higher mitochondrial volume densities (MVD) reflecting their more frequent activation. Mitochondria are essential for maintaining energetic support and cellular homeostasis. We hypothesized that to sustain higher MVD, mitochondrial biogenesis is higher in smaller compared to larger PhMNs. In female and male Sprague Dawley rats (~3 months of age) PhMNs were retrogradely labeled by intrapleural injection of cholera toxin B (CTB). After 3 days, mitochondria in the cervical spinal cord were labeled by subdural injection of MitoTracker Red. The cervical spinal cord was collected and labeled PhMNs and mitochondria were imaged by high-resolution confocal microscopy and reconstructed in 3D. As previously reported, we found a significant negative correlation between MVD and PhMN somal surface area. By immunohistochemistry, we found an increased nuclear to cytosolic ratio of pCREBS1333 in smaller PhMNs compared to larger PhMNs. PGC1α and TFAM expression was also higher in smaller PhMNs. These findings support size-dependent differences in pCREBS133–PGC1α–TFAM pathway promoting mitochondrial biogenesis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: Endothelial cell (EC) dysfunction, driven by comorbidities of heart failure with preserved ejection fraction (HFpEF), has emerged as a potential contributor to disease progression, yet the EC specific molecular mediators in HFpEF remain poorly defined. Purpose: To identify EC-specific molecular mediators that are involved in HFpEF and determine their functional roles in disease pathogenesis. Hypothesis: Based on omics analysis of a murine HFpEF model, we hypothesized that EC plasminogen activator inhibitor-1 (PAI-1) is a key mediator of HFpEF pathogenesis. Methods: Male RiboTagEC (Cdh5CreERT2+/Rpl22HA/+) mice were used in a HFpEF model induced by hypertensive/metabolic stresses (60% calories from lard and L-NAME 0.5 g/L in water) or administrated with normal water and diet as controls. Hearts and skeletal muscle were collected for both bulk RNA sequencing (Bulk-seq) and EC-specific translatome analysis using translating ribosome affinity purification assay followed by RNA-sequencing (TRAP-seq). The functional roles of EC PAI-1 were tested using male tamoxifen-inducible, endothelial specific PAI-1 knockout (Cdh5CreERT2+/PAI-1flox/flox, PAI-1iEC KO) and control mice (PAI-1flox/flox, PAI-1iEC+/+) subjected to HFpEF induction. Cardiac function was assessed by echocardiography, pressure–volume (PV) loop analysis, and treadmill exercise testing. Student’s t-test was used (p < 0.05). Results: Bulk-seq and EC-specific TRAP-seq identified PAI-1 as one of the most upregulated genes in both heart and skeletal muscle EC in HFpEF. Bulk-seq demonstrated a 2.5-fold change (FC, log 2 FC=1.35) increases in the heart and 12.2-fold increases (log 2 FC = 3.61) in the skeletal muscle. TRAP-seq showed a 1.75-fold change (log 2 FC=0.81) increases in the heart and 4.76-fold increases (log 2 FC = 2.25) in the skeletal muscle. These consistent findings led us to investigate the functional role of EC PAI-1 in the pathogenesis of HFpEF. With similar body weight (Control: 40±4 g, n=10; KO: 38±6 g, n=11; p=0.319) and ejection fraction (Control: 54±6 %, n=10; KO: 54±5 %, n=12; p=0.686), we found that PAI-1iEC KO mice exhibited improved diastolic function after 10 weeks of HFpEF induction. Specifically, echocardiography demonstrated a significant reduction in E/e′ in KO mice (Control: 27±4, n=10; KO: 24±3, n=12; p=0.018). PV analysis confirmed this improvement with lower end-diastolic pressure (Control: 19±2 mmHg, n=8; KO: 13±5 mmHg, n=10; p=0.009), reduced Tau (Control: 9.7±1.2 ms, n=8; KO: 8.6±1.0 ms, n=10; p=0.047), and a reduced EDPVR constant β (Control: 0.20±0.05, n=6; KO: 0.10±0.03, n=6; p=0.017). KO mice also exhibited improved treadmill running distance (Control: 179±35 m, n=10; KO: 214±40 m, n=12; p=0.043). Conclusion: Endothelial PAI-1 contributes to diastolic dysfunction and reduced exercise capacity in HFpEF. These findings highlight endothelial PAI-1 as a potential therapeutic target for HFpEF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Mitochondria are organelles essential for maintaining energetic support and cellular homeostasis. In phrenic motor neurons (PhMNs), mitochondria support the high level of activity necessary to sustain neuromotor control of the diaphragm muscle during breathing. Previously, we observed that small PhMNs recruited during breathing have higher mitochondrial volume density (MVD) compared to large PhMNs that are recruited infrequently during higher force airway clearance behaviors. In support, we also found that the maximum velocity of the succinate dehydrogenase activity (SDHmax) was higher in small PhMNs compared to large PhMNs. However, total mitochondrial volume was comparable across PhMNs of varying size. This suggests that the total ATP demands of PhMNs do not vary with size. The distribution of mitochondria likely reflects the demands of ATP consumption. In airway smooth muscle cells, mitochondria are not homogeneously distributed, with a higher density in the perinuclear region. In addition, mitochondria appear to be localized in close proximity to the endoplasmic reticulum (ER) most likely to support cytosolic and mitochondrial Ca 2+ regulation. The ER is also clustered in the perinuclear compartment of cells. Perinuclear clustering of mitochondria most likely reflects the higher ATP consumption close to the nucleus. We hypothesized that MVD is higher in the perinuclear region of PhMNs compared to more distal compartments. PhMNs of young (6 month), female and male Fisher 344 rats were retrogradely labeled by intrapleural injection of Alexa 488-conjugated cholera toxin B (CTB). Three days later, mitochondria were labeled by subdural injection of MitoTracker Red CMXRos. Spinal cord tissue was collected following transcranial perfusion with 4% paraformaldehyde, sectioned longitudinally at 70 µm, and mounted onto slides. Mosaics of labeled PhMNs and mitochondria were acquired in 3D (Z optical slices of 0.5 μm) using a 60x Plan Apo oil-immersion objective (NA 1.40). Using a concentric (10 mm) shell method for analysis, MVD was quantified relative to the distance relative to the nuclear membrane of PhMNs. Our results show a disproportionately higher MVD within the perinuclear region compared to more distal regions of PhMNs. This perinuclear distribution of mitochondria was found across PhMNs of varying size. These results suggest that energetic requirements of nucleus and ER are major drivers of mitochondrial biogenesis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Spontaneous coronary artery dissection (SCAD) is a common type of myocardial infarction in females under the age of 50 years, caused by sudden separation between the coronary arterial wall layers and/or hematoma. The SCAD patient population is mostly females (~80%) with few or no traditional cardiovascular disease risk factors (e.g., obesity, hypertension). Common triggers for SCAD include sympathoexcitatory stimuli, such as intense physical and emotional stress. This implicates the sympathetic nervous system in the pathophysiology of SCAD. Thus, we aimed to investigate sympathetic nervous system responses to mental stress in patients with a history of SCAD. We hypothesized that females with a history of SCAD exhibit a greater increase in muscle sympathetic nerve activity (MSNA) with acute exposure to mental stress compared to healthy females. Methods: Seven females with a history of SCAD (age: 48±9 yrs, BMI: 29±6 kg/m 2 ) and seven age- and BMI-matched healthy female controls (CON, age: 49±9 yrs, BMI: 26±6 kg/m 2 ) participated in the study (both p>0.05). MSNA was measured via peroneal microneurography during a 2-minute rest, a 5-minute Stroop Color Word Test aimed at inducing mental stress, and a 2-minute recovery. Heart rate (HR, 3-lead electrocardiography) and BP (finger photoplethysmography) were continuously recorded during each stage. Data are presented as an absolute change from rest (Δmean±SD). Two-way independent t-tests were used for statistical analyses. Results: Resting mean blood pressure (MBP, SCAD: 96±14 vs CON: 89±7 mmHg, p=0.27), heart rate (HR, SCAD: 56±11vs CON: 65±16 bpm, p=0.25), MSNA burst frequency (SCAD: 22±9 vs CON: 18±7 bursts/minute, p=0.40) and total MSNA (SCAD: 1135±471 vs CON: 951±245 au/min, p=0.41) were not different between the groups. During the Stroop Color Word Test, average changes in MBP (SCAD: Δ10±9 vs CON: Δ8±5 mmHg, p=0.67) and HR (SCAD: Δ11±7 vs CON: Δ14±5 bpm, p=0.35) were not different between the groups. Similarly, average changes in MBP (SCAD: Δ3±4 vs CON: Δ-2±5 mmHg, p=0.13) and HR (SCAD: Δ3±4 vs CON: Δ3±2 bpm, p=0.62) were not different during the recovery. Changes in MSNA burst frequency with the Stroop Color Word Test (SCAD: Δ1±7 vs CON: Δ6±7 bursts/minute, p=0.22) and recovery (SCAD: Δ0±5 vs CON: Δ4±4 bursts/minute, p=0.13) were not different between the groups. Total MSNA changes were also not different during the Stroop Color Word Test (SCAD: Δ267±335 vs CON: Δ606±432 au/min, p=0.15) and recovery (SCAD: Δ68±666 vs CON: Δ217±217 au/min, p=0.61) between the two groups. Conclusion: These preliminary data suggest that contrary to our hypothesis, sympathetic nervous system responses to acute mental stress exposure are not different between females with a history of SCAD and healthy females. Further investigation is needed to understand MSNA association with chronic stress exposure in females with a history of SCAD. Funding: NIH K23 HL155506 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.