High blood pressure (BP) and poor BP control are associated with a greater loss of cognitive function and brain structural integrity with aging. Since BP is partially regulated by the autonomic nervous system (ANS), ANS activity may have implications for maintaining brain health with aging. Interestingly, higher heart rate variability (HRV), a common noninvasive measure of ANS activity, has been associated with better overall cognitive function. However, few studies have assessed the association between HRV and brain structural integrity. To our knowledge, there are no current studies that have assessed whether HRV is associated with gray matter microstructural integrity. OBJECTIVE: To assess the association between HRV and brain stiffness using magnetic resonance elastography (MRE) in adults across the lifespan. We hypothesized that higher (“better”) HRV would be associated with higher (“better”) brain stiffness. METHODS: Young (22-29yr; n=10), middle-aged (51-63yr; n=23), and older adults (66-79yr; n=14) underwent supine resting electrocardiography for 5 minutes and MRE to assess whole-brain (WB) stiffness. LabChart’s built-in HRV module was used to measure HRV, including the standard deviation of RR intervals (SDRR), root mean square of successive differences (RMSSD), high frequency power (HF), low frequency power (LF), and LF:HF ratio. We assessed the association between age, HRV, and WB stiffness using Pearson (r) or Spearman’s (ρ) correlations. Regression analyses were performed with robust standard errors (HC3) to assess the relation of HRV with WB stiffness, controlling for age. HRV data that was not normally distributed was log transformed. RESULTS: Across the combined sample (22-79yr), as expected, age was negatively correlated with SDRR (ρ=-0.506, p< 0.001), RMSSD (ρ=-0.390, p=0.007), HF power (n.u.) (ρ=-0.374, p=0.010), and WB stiffness (ρ=-0.790, p< 0.001). Age was also positively correlated with LF:HF ratio (ρ=0.308, p=0.035) and tended to be positively correlated with LF power (n.u.) (ρ=0.263, p=0.074). WB stiffness was positively correlated with SDRR (r=0.338, p=0.020) and tended to be positively correlated with RMSSD (r=0.254, p=0.085) and HF power (n.u.) (r=0.271, p=0.066). However, when adjusting for age, SDRR, RMSSD, and HF power (n.u.) did not exhibit any significant associations with WB stiffness (all: p≥0.457), while age was a significant predictor of WB stiffness in all three models (p< 0.001). WB stiffness was not associated with LF power (n.u.) (r=-0.194, p=0.191) or LF:HF ratio (r=-0.204, p=0.169). CONCLUSION: HRV and WB stiffness were strongly associated with age; however, HRV was not associated with WB stiffness after adjusting for age. Longitudinal studies should be conducted to explore whether changes in autonomic function directly impact brain structural integrity and cognitive function. Supported by NIH grants, R01AG080052, P20GM113125, & P30GM145765, & AHA 24IAUST1199297. 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.

High blood pressure (BP) and BP variability are risk factors for cognitive decline and dementia, making mechanisms of BP regulation interesting targets to attenuate age-related cognitive decline. The cardiovagal baroreflex is essential in the beat-to-beat regulation of BP, and the responsiveness of this reflex, known as cardiovagal baroreceptor sensitivity (cBRS), is a common measure of cardiac autonomic function. cBRS declines (worsens) with age, and lower cBRS is associated with worse white matter integrity and cerebral perfusion and a higher risk of Alzheimer’s disease. However, no studies have investigated the association of cBRS with brain mechanical properties assessed by magnetic resonance elastography (MRE). OBJECTIVES: To investigate differences in cBRS and brain mechanics assessed by MRE across the lifespan and whether cBRS is associated with whole brain stiffness and damping ratio (DR). We hypothesized that cBRS and brain mechanics would worsen with age and that higher (better) cBRS would be associated with better brain mechanics. METHODS: Young (n=10, 3 men, 22-29 years), midlife (n=22, 11 men, 51-63 years), and older adults (n=14, 4 men, 66-79 years) underwent supine resting electrocardiography and finger photoplethysmography. cBRS was determined using the sequence method for all sequences (cBRSall), which included up sequences (systolic BP and R-R interval increase) and down sequences (systolic BP and R-R interval decrease). MRE was used to assess whole brain stiffness and DR. We used one-way ANOVA models with Bonferroni post-hoc comparisons to assess differences in cBRS and brain mechanics across the three age groups. We performed regression analyses with robust standard errors (HC3) to assess the relation of cBRSall with brain stiffness and DR, controlling for age. Data are presented as mean ± standard deviation. RESULTS: cBRSall was higher (better) in young adults (32.6 ± 13.3 ms/mmHg), compared to midlife (10.1 ± 3.8 ms/mmHg, p< 0.01) and older adults (11.8 ± 5.7 ms/mmHg, p< 0.01) with no differences between midlife and older adults (p=1.00). Brain stiffness was lower (worse) in older adults (2.56 ± 0.12 kPa) compared to young (2.89 ± 0.13 kPa, p< 0.01) and midlife adults (2.80 ± 0.15 kPa, p< 0.01) with no differences between young and midlife adults (p=0.25). Similarly, DR was higher (worse) in older adults (0.27 ± 0.01) compared to young (0.25 ± 0.01, p< 0.01) and midlife adults (0.26 ± 0.01, p=0.01) with no differences between young and midlife adults (p=0.64). Age was negatively correlated with brain stiffness (b=-0.0099, t=-4.68, p< 0.01), while cBRSall showed a marginal negative effect on brain stiffness (b=-0.0059, t=-1.98, p=0.054). Similarly, age was positively correlated with DR (b=0.0004, t=2.93, p< 0.01), while cBRSall was not a significant predictor of DR (p=0.18). CONCLUSION: cBRS and brain mechanics were strongly associated with age, but cBRS was not associated with better brain mechanics as hypothesized. This may be because cBRS but not brain mechanics were different between young and midlife adults, while brain mechanics but not cBRS were different between midlife and older adults. This suggests that cBRS may decline earlier in life than changes in brain mechanics, making it difficult to demonstrate an association in a cross-sectional cohort. Additional work is needed to determine the precise age ranges during which changes in autonomic function and brain mechanics occur, and future studies should utilize longitudinal designs to investigate whether cBRS and other vascular factors at younger ages have a causal impact on brain health later in life. Supported by NIH grants, R01AG080052, P20GM113125, & P30GM145765, & AHA 24IAUST1199297. 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: Endothelial dysfunction has emerged as a risk factor for many age-related diseases such as cardiovascular disease (CVD). Recently, pro-inflammatory T-lymphocytes (T-cells) have been identified as important mediators of endothelial dysfunction in multiple pre-clinical models. Pro-inflammatory and senescent T-cell subsets have also been associated with endothelial dysfunction in middle-aged adults with hypertension. However, the relationships between T-cell subpopulations and endothelial dysfunction have not been explored in large, population-based cohorts. Therefore, the purpose of this study was to evaluate the associations of T-cell populations with endothelial function in participants of the Multi-Ethnic Study of Atherosclerosis (MESA), an observational cohort study of adults free from CVD at the baseline exam (2000-02). Based on prior literature, we hypothesized that higher proportions of pro-inflammatory (CD4 + IFN-γ + ) and senescence-associated (CD4 + CD28 - CD57 + ) T-cells would be associated with lower endothelial function. Methods: Peripheral blood T-cell subpopulations were measured by flow cytometry using cryopreserved cells collected at the baseline Exam (N=968). Endothelial function was assessed at baseline using flow-mediated dilation (FMD) of the brachial artery by duplex ultrasound. Associations of T-cells, analyzed per 1-SD increment, with FMD were assessed using multivariable linear regressions with adjustment for CVD risk factors. The primary analysis examined associations between CD4 + IFN-γ + and CD4 + CD28 - CD57 + T-cells with FMD. A secondary analysis examined associations between 27 additional immune cell populations in MESA with FMD percent change, using an FDR p<0.05 to correct for multiple hypothesis testing. Results: CD4 + IFN-γ + and CD4 + CD28 - CD57 + T-cells were not significantly associated with FMD. In secondary analysis, higher pan CD4 + and CD8 + T-cells were significantly associated with lower (β=-0.4, P=0.0002, 95%CI=-0.6, -0.19) and higher (β=0.029, P=0.006, 95%CI=0.006) FMD percent change, respectively. Similar results were observed with absolute FMD. Conclusions: Thedata from a large multi-ethnic cohort study suggest that higher CD4 + and lower CD8 + T-cell proportions are associated with endothelial dysfunction as measured by FMD. The cross-sectional findings warrant additional longitudinal human studies, and greater T-cell phenotyping, to understand the influence of CD4 + and CD8 + T-cell balance on endothelial function. The research reported in this article was supported by R01HL120854, and R01HL135625 from the National Heart, Lung, and Blood Institute and T32AG033534. This abstract was presented at the American Physiology Summit 2025 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.

Aging is the primary risk factor for Alzheimer’s disease (AD) which is the most common cause of dementia. The risk factors for AD emerge during midlife and are similar to cardiometabolic diseases. Midlife cardiometabolic changes are worsened by poor lifestyle habits, such as consuming a Western Diet (WD), which is partially characterized by high added sugar intake (i.e., all caloric sweeteners added to food during cooking or processing). This study aimed to investigate if short-term consumption of excessive added sugars acutely alters cardiometabolic risk factors and hippocampal-dependent memory function in midlife adults (50-64 years old). We hypothesized that, compared to a low added sugar diet, the high added sugar diet would be detrimental to cardiometabolic and brain health. In a randomized order, 26 participants (10 males / 16 females) were assigned to consume a 10-day high-added sugar (HS: 25% total calories) and low- added sugar (LS: 5% total calories) diet. At the end of each diet, blood was sampled, blood pressure was measured, and memory recall was tested using the Hopkins Verbal Learning Test (HVLT) and the Brief Visuospatial Memory Test (BVMT). Compared to the LS diet, the HS diet significantly increased plasma triglycerides (LS: 91±31; HS: 102±30 mg/dL; p = 0.04) and mean arterial blood pressure (LS: 80±7; HS: 85±9 mmHg; p = 0.002). After the HS diet, total memory recall scores were significantly lower for BVMT: (LS: 26.0±5.2; HS 23.3±5.9 correct responses; p = 0.02) but not the HVLT. Compared to the LS diet, delayed memory recall scores were significantly lower after the HS diet for both tests [(HVLT: (LS: 10.5±1.5; HS 9.9±1.7 correct responses; p = 0.03) and BVMT: (LS: 10.1±1.6; HS 8.8±2.2 correct responses; p = 0.002)]. A short-term (10-day) diet with an excessive amount of added sugars increases cardiometabolic risk factors, whichmay make the brain susceptible to lower memory recall in otherwise healthy midlife adults. This study highlights the importance of diet on cardiometabolic and brain health in midlife adults. Future studies should examine the long-term impact of added sugars on AD risk and explore the underlying mechanisms by which added sugars contribute to cognitive aging.

Background: Endothelial dysfunction has emerged as a risk factor for many age-related diseases such as cardiovascular disease and Alzheimer’s disease and related dementias. T-lymphocytes (T-cells) have been identified as important regulators of endothelial function in multiple murine models, and pro-inflammatory and senescent T-cell subsets have been associated with endothelial dysfunction in middle-aged adults with hypertension. However, there is little data on the relationships between T-cell subsets and endothelial function in large, multi-ethnic, population-based cohorts free from cardiovascular diseases. Therefore, the purpose of this study was to determine whether T-cell subsets were associated with endothelial function in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery by duplex ultrasound at the baseline exam. Baseline peripheral blood T-cell subsets were measured using flow cytometry (N=968). Two analyses were employed. The primary analysis examined associations of Th1 (CD4 + interferon-γ + (IFN-γ + )) and CD4 + CD28 − CD57 + T-cells, specified as a priori hypotheses, with FMD using multivariable linear regression. Secondary analyses examined associations between 27 additional immune cell populations with FMD. Results: Th1 and CD4 + CD28 − CD57 + T-cells were not associated with FMD. In secondary analyses, a 1-SD higher value of pan CD4 + and pan CD8 + T-cells were associated with lower and higher FMD, respectively. Conclusions: These results may suggest regulation of endothelial function by T-cells in pre-clinical models is conserved in humans. The findings warrant additional longitudinal human studies with greater T-cell phenotyping to further understand the influence of CD4 + and CD8 + T-cell balance on endothelial function.

AbstractYoung individuals with post‐traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23 ± 3 years), and 13 age‐ and sex‐matched controls (CTRL) participated in the study. Exercise‐induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6 kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P = 0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6 kg: P < 0.01) by blunting elevated exercise‐induced MAP responses (3 kg: P = 0.01; 6 kg: P < 0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise‐induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance.

Aging is associated with reductions in cerebrovascular reactivity (CVR) and cerebrovascular conductance (CVC), which may contribute to the development of neurodegenerative disease and stroke. In the peripheral vasculature, increased oxidative stress is linked to vascular dysfunction and is ameliorated following infusion of the antioxidant ascorbic acid (AA). However, oxidative stress’ effect on cerebrovascular function in humans is not entirely understood. PURPOSE: To determine whether oxidative stress reduces CVR and CVC in middle-aged and older adults (MA/O). We hypothesized that AA infusion would increase CVR and CVC in MA/O but not young adults (YA). METHODS: Young (18-29 years) and middle-aged and older (55-79 years) adults were recruited for two identical experimental visits. Each visit consisted of the same measures performed both before and after the infusion of either AA or saline (SAL). Middle cerebral artery blood velocity (MCAv) was recorded using a transcranial Doppler ultrasound probe. CVR was tested using a hypercapnia protocol that was achieved with a computer-based gas blender that increased the subjects’ end-tidal partial pressure of carbon dioxide (PETCO2) 9 mmHg above baseline for a 3-minute period. CVR was defined as the percent change in MCAv during hypercapnia divided by the absolute change in PETCO2. CVC was defined as the percent of CVR normalized for the changes in mean arterial blood pressure. Two-way ANOVAs were used to assess the effects of AA and SAL on CVR and CVC. Fisher’s LSD tests were used to assess main and interaction effects when necessary. RESULTS: 8 YA (25 + 2 years) and 14 MA/O (65 + 6 years) completed the experimental visits. There was a significant main effect of condition (pre/post) on CVR following SAL infusion (p = 0.016), and a significant age x condition interaction effect on CVR following AA infusion (p = 0.016). There were no significant main or interaction effects on CVC following SAL infusion, but there was a significant age x condition interaction effect on CVC following AA infusion (p = 0.012). Post hoc testing indicated that the difference in CVR following SAL infusion was due to an increase in YA (3.0 + 0.5 %/mmHg pre vs. 3.8 + 1.1 %/mmHg post, p = 0.047), whereas the difference in CVR following AA infusion was due to an increase in MA/O (3.3 + 1.7 %/mmHg pre vs. 4.1 + 1.9 %/mmHg post, p = 0.006). The difference in CVC was indicated to be due to both lower baseline CVC in MA/O (2.3 + 0.4 %/mmHg YA pre vs. 1.3 + 1.1 %/mmHg MA/O pre, p = 0.019) and an increase in CVC in MA/O following AA infusion (1.3 + 1.1 %/mmHg pre vs. 2.0 + 0.5 %/mmHg post, p = 0.047). CONCLUSION: Our main finding is that AA infusion restores CVR and CVC in MA/O, but not YA. This finding suggests that age-related increases in oxidative stress may impair cerebrovascular function. Supported by NIH Grant P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prior research has investigated the association of cardiovagal baroreceptor sensitivity (BRS) with white matter neuronal integrity and cerebral perfusion using magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI) and arterial spin labeling (ASL); however, less is known about the association with specific regions of gray matter (i.e, hippocampus) involved in memory formation and recall. MR elastography (MRE) has emerged as a constructive tool for assessing the viscoelastic mechanical properties of the brain which are believed to reflect the microstructural integrity of neuronal tissue. PURPOSE: To investigate the association between cardiovagal BRS and the viscoelastic properties of the brain, with a sub goal of examining how advanced age affects this association. We hypothesized that there would be a positive relation between cardiovagal BRS and hippocampal (HC) viscoelastic properties that strengthens with age, indicating a greater influence of blood pressure control on HC microstructural integrity. Methods: Ten young (Yng, 25 ± 2 years) and ten middle-aged adults (MA, 55 ± 3 years) laid in supine position for 10 minutes while arterial blood pressure (ABP) and heart rate (HR) were measured. R-R intervals and systolic blood pressures were plotted within a linear regression to calculate the spontaneous baroreflex slope. Subjects went in an MRI scanner to measure hippocampal viscoelastic properties using MRE. Results: As expected, we observed a lower cBRS in the middle-aged group compared with young (MA: 12.51±4.41 vs. Yng: 25.21±8.77 ms/mmHg, p≤0.05). There were no significant differences in HC stiffness or damping ratio when comparing between age groups (MA: 3.06±0.32 kPa vs. Yng: 3.02±0.09 kPa, p=0.69; MA: 0.2±0.02 vs. Yng: 0.2±0.03, p=0.56). However, a multiple linear regression with age included as a categorical covariate revealed a trend towards a stronger association between HC stiffness and cBRS in the middle-aged compared to the young group (p=0.07). CONCLUSION: In contrast to our hypothesis, preserved BRS was associated with lower HC stiffness in the middle-aged group; however, the physiological importance of this finding needs to be more completely explored. Our findings indicate that the association between short-term blood pressure regulation via cardiovagal BRS may be more closely linked to HC tissue integrity with advancing age. These mechanisms should be explored in a larger cohort including older individuals. Supported by UD Research Foundation 2020 Pilot Grant and P20GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ObjectivesTo assess the reliability and validity of measuring resting cerebral blood flow (CBF) and hippocampal CBF using a single-post-labeling delay (PLD) and a multi-PLD pseudo-continuous arterial spin labeling (pCASL) protocol for cerebrovascular reactivity (CVR) testing.Methods25 healthy, midlife adults (57 ± 4 years old) were imaged in a Siemens Prisma 3T magnetic resonance imaging (MRI) scanner. Resting CBF and hippocampal CBF were assessed using two pCASL protocols, our modified single-PLD protocol (pCASL-MOD) to accommodate the needs for CVR testing and the multi-PLD Human Connectome Project (HCP) Lifespan protocol to serve as the reference control (pCASL-HCP). During pCASL-MOD, CVR was calculated as the change in CBF from rest to hypercapnia (+9 mmHg increase in end-tidal partial pressure of carbon dioxide [PETCO2]) and then normalized for PETCO2. The reliability and validity in resting gray matter (GM) CBF, white matter (WM) CBF, and hippocampal CBF between pCASL-MOD and pCASL-HCP protocols were examined using correlation analyses, paired t-tests, and Bland Altman plots.ResultsThe pCASL-MOD and pCASL-HCP protocols were significantly correlated for resting GM CBF [r = 0.72; F (1, 23) = 25.24, p < 0.0001], WM CBF [r = 0.57; F (1, 23) = 10.83, p = 0.003], and hippocampal CBF [r = 0.77; F (1, 23) = 32.65, p < 0.0001]. However, pCASL-MOD underestimated resting GM CBF (pCASL-MOD: 53.7 ± 11.1 v. pCASL-HCP: 69.1 ± 13.1 mL/100 g/min; p < 0.0001), WM CBF (pCASL-MOD: 32.4 ± 4.8 v. pCASL-HCP: 35.5 ± 6.9 mL/100 g/min; p = 0.01), and hippocampal CBF (pCASL-MOD: 50.5 ± 9.0 v. pCASL-HCP: 68.1 ± 12.5 mL/100 g/min; p < 0.0001). PETCO2 increased by 8.0 ± 0.7 mmHg to induce CVR (GM CBF: 4.8% ± 2.6%; WM CBF 2.9% ± 2.5%; and hippocampal CBF: 3.4% ± 3.8%).ConclusionOur single-PLD pCASL-MOD protocol reliably measured CBF and hippocampal CBF at rest given the significant correlation with the multi-PLD pCASL-HCP protocol. Despite the lower magnitude relative to pCASL-HCP, we recommend using our pCASL-MOD protocol for CVR testing in which an exact estimate of CBF is not required such as the assessment of relative change in CBF to hypercapnia.

Chronic consumption of a Western diet (WD), high in added sugars and saturated fat (SFA) and low in fiber, contributes to increased cardiometabolic risk parameters, including elevated serum lipids and uric acid (UA). Additionally, long-term WD consumption is negatively associated with cognitive function and brain health. Reductions in cerebral blood flow (CBF) have been observed following acute dietary added sugar and SFA intake; however, the direct acute effects of a Western-style meal on cerebrovascular function and the underlying mechanisms are not fully understood. The purpose of this study was to determine the effects of a single Western-style meal on serum lipids and UA along with cerebrovascular function in healthy young and middle-aged adults. 11 participants [6M/5F, age: 45±14 y (range: 30-64 y); BMI: 26±3 kg/m 2 ; BP: 118±12/74±6 mmHg] were enrolled in this randomized-controlled crossover trial. Participants were randomized to two meals that were similar in total energy (~1280 kcal) and macronutrient content. The experimental WD meal consisted of 61 g added sugars, 26 g SFA (60 g total fat), and 5 g fiber, while the control meal (CM) consisted of 16 g added sugars, 12 g SFA (60 g total fat), and 19 g fiber. Serum lipids and UA were assessed at baseline and 3 hours after consumption of each meal. Cerebrovascular reactivity (CVR) was measured at both timepoints and was assessed as the maximal % change in gray matter CBF during 3-minutes of hypercapnia. CBF was measured using pseudo-continuous arterial spin labeling (PCASL) with a single post-labeling delay and was acquired using a Siemens 3T Prisma MRI scanner. A 2x2 repeated measures ANOVA was used to quantify serum lipids and UA pre- and post-consumption of each meal. An unpaired Mann-Whitney test was used to assess post-meal changes in CVR following the WD meal and CM. Serum triglyceride (Time: p=0.0003; Meal: p=0.57; Interaction: p=0.97) and VLDL-C concentrations (Time: p=0.0005; Meal: p=0.55; Interaction: p=0.81) were higher while HDL-C (Time: p<0.0001; Meal: p=0.17; Interaction: p=0.55) and LDL-C (Time: p=0.0004; Meal: p=0.26; Interaction: p=0.94) were lower after consuming each meal with no main or interaction effect of meal type. Serum UA concentration was reduced following both meals with a greater decrease following the WD meal (Time: p<0.0001; Meal: p=0.35; Interaction: p=0.03). Post-meal % Δ CVR was increased following the WD meal compared to CM [WD (N=10): 1.88 ± 2.86% vs. CM (N=7): -0.31 ± 0.46%; p=0.03]. These results suggest serum UA concentration is reduced and CVR is increased after acute consumption of a WD meal. Future studies should explore the interaction between UA metabolism and cerebrovascular function following an acute WD meal to better understand the mechanism behind the negative association between chronic WD consumption and cognitive function. Grant Support: NIH grants P20GM103653, P20GM113125, K01AG054731 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Purpose: Young non-Hispanic black (BL) males have displayed lower blood flow (BF) and vascular conductance (VC), but intact functional sympatholysis, during upper limb exercise when compared to non-Hispanic white (WH) males. This study sought to explore if similar differences were also present in the lower limbs.Methods: Thirteen young BL males and thirteen WH males completed one visit comprised of rhythmic lower limb (plantar flexion) exercise as well as upper limb (handgrip) exercise for a limb-specific comparison. Limb BF, mean arterial pressure (MAP), and VC were evaluated at three submaximal workloads (8, 16, and 24 kg). To determine potential limb differences in functional sympatholysis, the impact of sympathetic nervous system activation (via cold-pressor test (CPT)) was evaluated at rest and during steady state exercise (30 % of maximal voluntary contraction) on a subsequent visit.Results: MAP responses to lower and upper limb exercise were elevated in young BL males (vs WH males), resulting in significantly lower VC responses in the upper limb, but not the lower limb. Further, BL males, when compared to WH males, revealed no differences in functional sympatholysis, evident by similar responses in both the exercising leg and arm VC during CPT.Conclusion: The findings of the current study indicate that although elevated MAP responses were observed during both lower and upper limb exercise in young BL males, vascular conductance was only hindered in the upper limbs. This may potentially highlight enhanced compensatory mechanisms in the lower limb (vs upper limb) to maintain perfusion in young BL males.

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Objective: We developed a modified pseudo-continuous arterial spin labeling (pCASL) sequence for measuring cerebrovascular reactivity (CVR) to hypercapnia in humans; however, the method has yet to be validated against an established pCASL sequence for assessing brain perfusion at rest. The purpose of this project was to compare resting brain perfusion from our modified sequence (Rest-CVR) to the pCASL sequence developed by the Human Connectome Project (HCP). The secondary purpose was to determine the association of these pCASL sequences with lipid biomarkers. Methods: Resting brain perfusion was assessed using both sequences in 7 middle-aged adult participants (56 ± 5 years old) using a 64-channel head coil inside a Siemens Prisma 3T MRI scanner. The modified Rest-CVR sequence included a shorter scan time (~3 minutes) with a single post-labeling delay and duration of 1800ms, FOV= 215mm 2 , slice thickness 2.27mm, TR=4510ms, and TE=20ms. Blood samples were also collected to determine the association of each sequence with circulating lipid biomarkers to test the sensitivity of each sequence to clinically relevant risk factors of cerebrovascular disease. Results: Outcomes from the two pCASL sequences were significantly correlated [R 2 = 0.88; F (1,5) = 35.06 p = 0.002]. However, resting brain perfusion from Rest-CVR was significantly lower than HCP [Rest-CVR: 58.84 ± 15.22 vs. HCP: 81.12 ± 12.54 ml/min/100g; p = 0.0008]. Resting brain perfusion measurements from both sequences were negatively associated with low density lipoprotein (LDL) cholesterol (HCP: r = -0.97; p = 0.0001 and Rest-CVR: r = -0.87; p = 0.008) suggesting sensitivity of both to a clinically relevant risk factor for cerebrovascular disease. However, neither sequence was associated with total cholesterol, triglycerides, or high-density lipoprotein (HDL) cholesterol (p>0.05 for all). Conclusion: Rest-CVR was determined to be a reliable measure of resting brain perfusion in that it correlated with the HCP protocol; however, the lower magnitude relative to HCP makes it a less valid approach for accurately determining brain perfusion. Resting brain perfusion from both sequences was negatively associated with LDL suggesting both are sensitive to clinically relevant outcomes. The shorter Rest-CVR sequence may be most suitable for studies in which an exact estimate of brain perfusion is not required such as when assessing a relative change to hypercapnia. Grant Support: NIH/NIGMS - P20 GM113125 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

This study examined if high sodium (HS) intake in salt resistant (SR) individuals attenuates brachial artery (BA) flow-mediated dilation in response to reactive (occlusion) and active (exercise) hyperemia. In SR individuals, HS intake impaired reactive hyperemia-induced BA dilation, but not exercise-induced BA dilation. This finding suggests that although brachial artery nitric oxide bioavailability may be reduced following HS intake, the redundant mechanisms associated with adequate upper limb blood flow regulation during exercise are maintained.

PURPOSE:Adequate, robust vascular responses to passive and active movement represent two distinct components linked to normal, healthy cardiovascular function. Currently, limited research exists determining if these vascular responses are altered in premenopausal females (PMF) when compared across sex or menstrual cycle phase. METHODS:Vascular responses to passive leg movement (PLM) and handgrip (HG) exercise were assessed in PMF ( n = 21) and age-matched men ( n = 21). A subset of PMF subjects ( n = 11) completed both assessments during the early and late follicular phase of their menstrual cycle. Microvascular function was assessed during PLM via changes in leg blood flow, and during HG exercise, via steady-state arm vascular conductance. Macrovascular (brachial artery [BA]) function was assessed during HG exercise via BA dilation responses as well as BA shear rate-dilation slopes. RESULTS:Leg microvascular function, determined by PLM, was not different between sexes or across menstrual cycle phase. However, arm microvascular function, demonstrated by arm vascular conductance, was lower in PMF compared with men at rest and during HG exercise. Macrovascular function was not different between sexes or across menstrual cycle phase. CONCLUSIONS:This study identified similar vascular function across sex and menstrual cycle phase seen in microvasculature of the leg and macrovascular (BA) of the arm. Although arm microvascular function was unaltered by menstrual cycle phase in PMF, it was revealed to be significantly lower when compared with age-matched men highlighting a sex difference in vascular/blood flow regulation during small muscle mass exercise.

Contrary to our hypothesis, young individuals with GAD demonstrated similar macro- and microvascular function as well as similar whole blood oxidant production when compared to age- and sex-matched individuals without GAD. This may highlight preserved cardiovascular health in young individuals with GAD.

This study revealed no differences in PLM-induced LBF responses in premenopausal females when compared to age-matched males or when assessed across follicular menstrual cycle phases.

Purpose: Lower limb microvascular dysfunction resulting from prolonged sitting (PS) bouts has been revealed to occur independent of sex. Although acute antioxidant supplementation has been reported to blunt conduit artery dysfunction following PS in young males, it is unknown if this protective effect extends to the microvasculature or is relevant in young females, who possess intrinsic vascular protective mechanisms specific to antioxidant defense. Therefore, this study employed an acute antioxidant supplementation to further examine sex differences during PS with a specific focus on microvascular function. Methods: On two separate visits, 14 females (23 +/- 3 years) and 12 males (25 +/- 4 years) had leg microvascular function (LMVF) assessed (via the passive leg movement technique) before and after 1.5 h of sitting. Prior to each visit, one gram of vitamin C (VC) or placebo (PL) was consumed. Results: PS significantly reduced LMVF [PL: (M:-34 +/- 20; F:-23 +/- 18%; p < 0.01) independent of sex (p = 0.7)], but the VC condition only blunted this reduction in males (VC:-3 +/- 20%; p < 0.01), but not females (VC:-18 +/- 25%; p = 0.5). Conclusion: Young males and females reported similar reductions LMVF following PS, but only the young males reported a preservation of LMVF following the VC supplementation. This finding in young females was highlighted by substantial variability in LMVF measures in response to the VC condition that was unrelated to changes in the potential contributors to sitting-induced reductions in LMVF (e.g. lower limb venous pooling, reduced arterial shear rate). New and noteworthy: In this study, we employed an acute Vitamin C (VC) supplementation to examine sex differences in leg microvascular function (LMVF) following a bout of prolonged sitting. This study revealed that prolonged sitting reduced LMVF independent of sex, but only young males reported an attenuation to this lowered LMVF following VC supplementation. The young females revealed substantial variability in sitting induced changes to LMVF that could not be explained by the potential contributors to sitting-induced reductions in LMVF (e.g. lower limb venous pooling, reduced arterial shear rate).