Changes In Blood Pressure Research Articles

Postural effects on blood pressure, intraocular pressure, and ocular perfusion pressure in patients with spinal cord injury

Background Reduced ocular perfusion pressure (OPP) from hypotension and consistent OPP variability due to blood pressure (BP) fluctuations are predisposing factors for glaucoma. Low resting BP and orthostatic hypotension (OH) in spinal cord injury (SCI) patients may increase the risk of glaucoma post-injury. This study investigated BP, intraocular pressure (IOP), and OPP changes between supine and sitting positions in SCI and normal individuals. Methods Twenty SCI cases (high paraplegia, T1–T6 n = 6; low paraplegia, T7–L3 n = 14) and matched controls (1:1) were included. Systolic and diastolic BP (SBP and DBP) were measured digitally, and IOP with rebound tonometry. Measurements were taken one minute apart in both positions. Mean arterial pressure (MAP) was calculated, and OPP was determined using position-specific formulas. Results No SCI subjects exhibited OH. Both groups experienced significant BP increment (P < 0.05) from supine to sitting. SBP increased by 4.4 ± 8.4 mmHg (SCI) and 3.6 ± 6.2 mmHg (normal), while DBP increased by 4.2 ± 5.1 mmHg (SCI) and 6.7 ± 5.5 mmHg (normal). IOP and OPP decreased significantly (P < 0.05) after postural change in both groups, yet differences between them were not significant. Analysis by injury level revealed lower parameter values in high paraplegia than in low paraplegia, with the latter group showing a more significant reduction in OPP after postural change. Conclusion Postural changes differently affect BP, IOP, and OPP in SCI compared to normal individuals, with variations based on the level of SCI. While not directly assessing glaucoma, the study offers insights into ocular hemodynamics in SCI compared to normals.

Efficacy of Magnesium Sulfate and Labetalol in the Treatment of Pregnancy-Induced Hypertension and Its Effect on Anxiety and Depression: A Retrospective Cohort Study.

In this study, the effect of magnesium sulfate and labetalol in treating pregnancy-induced hypertension (PIH) and its influence on anxiety and depression in patients are observed, and new ideas for treating anxiety and depression in PIH are introduced. A retrospective cohort study was conducted to select patients with PlH diagnosed from July 2020 to July 2023 from Affiliated Hospital of Electronic Science and Technology University and Chengdu Women' s and Children's Central Hospital in Chengdu of Sichuan Province. The changes in blood pressure, Edinburgh Postnatal Depression Scale (EPDS), and generalized anxiety disorder 7 (GAD-7) in patients with hypertensive pregnancy were collected and analyzed. In our investigation, 219 patients completed the study, and 36.1% (79/219) of them developed anxiety and depression. According to whether the patients were treated with magnesium sulfate and labetalol, 49 cases were assigned to the magnesium sulfate and labetalol treatment (MSLT) group, and 30 cases were assigned to the conventional treatment (CT) group. Edinburgh Postnatal Depression Scale scores and GAD-7 scores in the MSLT group were significantly lower than those in the CT group, indicating that magnesium sulfate and labetalol can improve anxiety and depression in hypertensive patients during pregnancy. The difference was statistically significant (P < .05). According to the changes in systolic blood pressure, the clinical efficacy of patients was evaluated, and no significant difference in efficacy existed between the MSLT and CT groups. Magnesium sulfate and labetalol can control the blood pressure of patients with PIH and indirectly improve anxiety and depression in patients with PIH, thereby introducing new ideas for the treatment of PIH accompanied by anxiety and depression.

Safety and Efficacy of 2.5 mg and 1.25 mg Nebulized Salbutamol Compared with Placebo on Transient Tachypnea of the Newborns: A Triple-Blind Phase II/III Parallel Randomized Controlled Trial.

Background: To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. Methods: We conducted a triple-blind, phase II/III parallel randomized controlled trial in two university-affiliated hospitals with neonatal intensive care units. Newborns with a confirmed diagnosis of TTN, with gestational age >35 weeks and gestational weight >2 kg were included. Cases of asphyxia, meconium aspiration syndrome, and persistent pulmonary hypertension were excluded. Ninety eligible patients were randomly allocated in three intervention groups (2.5 mg salbutamol, 1.25 mg salbutamol, and placebo), and a single-dose nebulized product was prescribed 6 hours after the birth. Safety outcomes included postintervention tachycardia, hyperglycemia, hypokalemia, and changes in blood pressure. To evaluate the efficacy, the duration of postintervention tachypnea, TTN clinical score, and clinical and paraclinical respiratory indices were assessed. Parents, Outcome assessors, and data analyzer were blind to the intervention. Results: There was no adverse reaction, including tachycardia, hypokalemia, and jitteriness. Both groups of salbutamol recipients showed significant improvement regarding respiratory rate, TTN clinical score, and oxygenation indices compared with the placebo (p-values <0.001). Nonstatistically significant higher hospital stay was observed in the placebo group. Single 2.5 mg salbutamol nebulization showed a little better outcome than the dose of 1.25 mg, although we could not find statistical superiority. Conclusion: The newly applied single high dose of 2.5 mg nebulized salbutamol is safe in treating TTN and leads to notable faster improvement of respiratory status without any considerable adverse reaction. Registry code: IRCT20190328043133N1.

Non-invasive pulse arrival time as a surrogate for oscillometric systolic blood pressure changes during non-pharmacological intervention

Background. Non-invasive continuous blood pressure (BP) monitoring is of longstanding interest in various cardiovascular scenarios. In this context, pulse arrival time (PAT), i.e., a surrogate parameter for systolic BP (change), became very popular recently, especially in the context of cuffless BP measurement and dedicated lifestyle interventions. Nevertheless, there is also understandable doubt on its reliability in uncontrolled and mobile settings. Objective. The aim of this work is therefore the investigation whether PAT follows oscillometric systolic BP readings during moderate interventions by physical or mental activity using a medical grade handheld device for non-invasive PAT assessment. Approach. A study was conducted featuring an experimental group performing a physical and a mental task, and a control group. Oscillometric BP and PAT were assessed at baseline and after each intervention. Interventions were selected randomly but then performed sequentially in a counterbalanced order. Multivariate analyses of variance were used to test within-subject and between-subject effects for the dependent variables, followed by univariate analyses for post-hoc testing. Furthermore, correlation analysis was performed to assess the association of intervention effects between BP and PAT. Main results. The study included 51 subjects (31 females). Multivariate analysis of variances showed that effects in BP, heart rate, PAT and pulse wave parameters were consistent and significantly different between experimental and control groups. After physical activity, heart rate and systolic BP increased significantly whereas PAT decreased significantly. Mental activity leads to a decrease in systolic BP at stable heart rate. Pulse wave parameters follow accordingly by an increase of PAT and mainly unchanged pulse wave analysis features due to constant heart rate. Finally, also the control group behaviour was accurately registered by the PAT method compared to oscillometric cuff. Correlation analyses revealed significant negative associations between changes of systolic BP and changes of PAT from baseline to the physical task (−0.33 [−0.63, 0.01], p < 0.048), and from physical to mental task (−0.51 [−0.77, −0.14], p = 0.001), but not for baseline to mental task (−0.12 [−0,43,0,20], p = 0.50) in the experimental group. Significance. PAT and the used digital, handheld device proved to register changes in BP and heart rate reliably compared to oscillometric measurements during intervention. Therefore, it might add benefit to future mobile health solutions to support BP management by tracking relative, not absolute, BP changes during non-pharmacological interventions.

Immune Metabolic Reprogramming by Excess Dietary Salt in Salt Sensitive Hypertension via CXCL8

Salt sensitivity of blood pressure (SSBP) is when blood pressure changes parallel to salt loading/ depletion and is an independent risk factor for cardiovascular disease. Despite its importance, there is no feasible diagnosis, which limits investigational studies to identify therapeutic targets. We have found that immune cells mediate SSBP via Epithelial Sodium Channel (ENaC). CXCL8/(IL-8), a known chemoattractant plays a well-known role in glycolysis. We hypothesize that CXCL8 mediates immune metabolic reprogramming of immune cells to glycolysis via ENaC. To test this hypothesis, we performed bulk and single cell RNA sequencing in human monocytes from individuals from a modified Weinberger inpatient salt loading/ depletion protocol. The participants were instructed to refrain from taking their blood pressure medication for 2 weeks prior to the salt loading/depletion protocol. Blood and urine samples were collected, as well as ambulatory blood pressure recording. We found that changes in immune cell activation via isolevuglandin (IsoLG) protein-adducts mirror changes in salt balance and blood pressure in salt sensitive but not salt resistant individuals. We confirmed that these in vivo changes can be recapitulated in vitro. In addition, we found that salt-loading both in vivo and in vitro increases antigen presenting cell production of IL-8, which was reversed after salt depletion in salt sensitive, but not salt resistant people. ENaC inhibition by amiloride prevented the high salt-induced production of IL-8. Moreover, high salt induced blood pressure changes of expression of CXCL8 (p = 0.01553, r = 0.8067) were significant along with varying expression of glycolytic genes, including hexokinase 1(HK1)(p = 0.04190, r = -0.7249), phosphofructokinase (PFKP)(p = 0.05932, r = 0.6879) and galactose mutarotase (GALM) (p = 0.04176, r = 0.5138). Seahorse analysis revealed increased extracellular acidification rate (ECAR) in high salt conditioned monocytes, which was associated with mitochondrial dysfunction. Our results suggest that high salt intake reprograms antigen presenting cell metabolism to glycolysis via IL-8 signaling. Furthermore, targeting IL-8 and mitochondrial switching to glycolysis may not only provide novel therapeutic approaches, but also important biomarkers for diagnosis of salt sensitivity of blood pressure. 1R03HL155041-01 (Kirabo, PI), 1R01HL144941-01A1 (Kirabo, PI), 5R01HL147818-22 (Kleyman &amp; Kirabo), 1R01HL157584-01 (Shibao, Kirabo — MPI), R01DK135764 (Kon, Shelton, Kirabo — MPI), R21TW012635 (Kirabo, Masenga — MPI), Meharry Medical College: School of Graduate Studies T32AI007281, T32GM14492, andT32HL00773. 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.

CiGNN: A Causality-Informed and Graph Neural Network Based Framework for Cuffless Continuous Blood Pressure Estimation.

Causalityholds profound potentials to dissipate confusion and improve accuracy in cuffless continuous blood pressure (BP) estimation, an area often neglected in current research. In this study, we propose a two-stage framework, CiGNN, that seamlessly integrates causality and graph neural network (GNN) for cuffless continuous BP estimation. The first stage concentrates on the generation of a causal graph between BP and wearable features from the the perspective of causal inference, so as to identify features that are causally related to BP variations. This stage is pivotal for the identification of novel causal features from the causal graph beyond pulse transit time (PTT). We found these causal features empower better tracking in BP changes compared to PTT. For the second stage, a spatio-temporal GNN (STGNN) is utilized to learn from the causal graph obtained from the first stage. The STGNN can exploit both the spatial information within the causal graph and temporal information from beat-by-beat cardiac signals for refined cuffless continuous BP estimation. We evaluated the proposed method with three datasets that include 305 subjects (102 hypertensive patients) with age ranging from 20-90 and BP at different levels, with the continuous Finapres BP as references. The mean absolute difference (MAD) for estimated systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 3.77 mmHg and 2.52 mmHg, respectively, which outperformed comparison methods. In all cases including subjects with different age groups, while doing various maneuvers that induces BP changes at different levels and with or without hypertension, the proposed CiGNN method demonstrates superior performance for cuffless continuous BP estimation. These findings suggest that the proposed CiGNN is a promising approach in elucidating the causal mechanisms of cuffless BP estimation and can substantially enhance the precision of BP measurement.

The impact of a single high-fat meal on indices of cerebrovascular function &amp; health

High-fat diets contribute to elevated risk for cardiovascular, cerebrovascular, metabolic, and neurocognitive diseases with reduced vascular health being a contributing factor. It is well documented that a single high-fat meal (HFM) reduces peripheral vascular function. Despite the elevated risk for/prevalence of cerebrovascular and neurocognitive disease with a high-fat diet, the impact of a single HFM on cerebrovascular function/health is less known. Cerebrovascular pulsatility index (PI) (measure of cerebral vascular stiffness) and cerebral autoregulation (ability of the cerebral vasculature to maintain constant blood flow during changes in arterial blood pressure) are indices of cerebral vascular function/health that are impaired in populations with elevated disease risk. To our knowledge, the impact of a HFM on these indices have not been studied. Accordingly, this study tested the hypothesis that a single HFM will blunt cerebrovascular function/health as indexed by increased PI and transfer function gain. Methods: Fifteen individuals (13 male; age: 28±11yr; BMI: 24±4 kg/m²) participated. Measures were made before and 2hr post-consumption of a HFM (990 kcal, 55g fat, 89g CHO, 35 g protein, 2120 mg sodium) which was purchased from McDonald’s. The HFM consisted of the following: 1 Sausage Biscuit, 1 Egg McMuffn, 2 hash browns, and 1 bottle of water. Continuous measures of beat-to-beat blood pressure and middle cerebral artery blood velocity (MCAV) were obtained during a minimum of 6-min quiet supine rest. Pulsatility index (measure of cerebrovascular stiffness) was calculated as MCAVsystolic − MCAVdiastolic / MCAVmean. Cerebral autoregulation was calculated as transfer function gain between spontaneous beat-to-beat changes in mean blood pressure and MCAVmean. Results: Cerebrovascular stiffness (PI) was increased following the HFM (pre: 0.81±0.12, post: 0.92±0.15; p&lt;0.001). Cerebrovascular autoregulation indexed as transfer function gain was elevated following the HFM in the very low, low, and high frequency ranges ( p=0.01 for all). Pulsatility index and transfer function gain were correlated in the low frequency range before (R=0.77, p&lt;0.01) and after (R=0.64, p=0.02) the HFM. Conclusion: These preliminary data indicate that a single HFM reduces indices of cerebral vascular function/health. Lastly, there is a positive relationship between PI and transfer function gain. Future work will continue to build upon these findings in a larger data set and will consider the impact of long-term exposure to a traditional HFM diet. Funding: The University of Texas at Arlington College of Nursing and Health Innovation and Institutional Start up Funds to Dr. Brothers. 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.

Ovariectomy-Induced Arterial Stiffening Differs From Vascular Aging and Is Reversed by GPER Activation.

Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging and whether activation of the G-protein-coupled estrogen receptor could reverse stiffness. Female C57Bl/6J mice were ovariectomized at 10 weeks of age or aged to 52 weeks, and some mice were treated with G-protein-coupled estrogen receptor agonists. Ovariectomy and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while ovariectomy increased material stiffness without altering vascular geometry. RNA-sequencing analysis revealed that ovariectomy downregulated smooth muscle contractile genes. The enantiomerically pure G-protein-coupled estrogen receptor agonist, LNS8801, reversed stiffness in ovariectomy mice to a greater degree than the racemic agonist G-1. In summary, ovariectomy and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling, while ovariectomy-induced material stiffness independent of geometry and a loss of the contractile phenotype. This study enhances our understanding of the impact of estrogen loss on vascular health in a murine model and warrants further studies to examine the ability of LNS8801 to improve vascular health in menopausal women.

Neuraminidase-3 Inhibition Improves Vascular Function in Diabetic Mice

In type 2 diabetes (T2D), endothelial dysfunction and arterial stiffening play a significant role in the development of cardiovascular disease. A central mediator of vascular dysfunction is degradation of the endothelial glycocalyx, a semipermeable mechanosensitive structure that separates the endothelium from the flow of blood and shear forces associated with it. Neuraminidase, a sialidase that cleaves sialic acid from the terminal branches of glycoproteins and glycolipids, is implicated in glycocalyx degradation. However, its role in mediating vascular dysfunction in the setting of T2D remains relatively unexplored. Herein, we tested the hypothesis that pharmacological inhibition of neuraminidase-3 (Neu3i) improves glycocalyx integrity, ameliorates endothelial dysfunction, and reduces arterial stiffness in diabetes. In support of this hypothesis, we report that, relative to vehicle-treated cells, endothelial cells exposed to Neu3i for 24hr have increased glycocalyx components including sialic acid and N-acetylglucosamine (GlcNAc), one of the amino sugars comprising the N-acetyllactosaminoglycans chains within the glycocalyx, as assessed with fluorescent lectin staining using MAA/Mal I+2 and WGA, respectively. We further show that treatment of diabetic ( i.e., db/db) mice with Neu3i for 28 days reduced aortic pulse wave velocity, with no change in blood pressure, when compared to vehicle-treated mice. Neu3i also reduced the stiffness of aortic explants, as assessed via atomic force microscopy. Excised arteries were also assessed for flow-mediated dilation and vascular stiffness using pressure myography. Diabetic mice treated with Neu3i had increased flow-mediated dilation and reduced incremental modulus of elasticity, indicative of improved endothelial function and reduced arterial stiffness. Collectively, these data support the hypothesis that Neu3 is a potential therapeutic target for the amelioration of vascular dysfunction in T2D. National Institutes of Health grant: R01HL153264 to LM-L and JP. 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.

Spontaneous Bursts of Muscle Sympathetic Nerve Activity Reduce Femoral Arterial Compliance in Humans

Previous studies in rodents have demonstrated tonic sympathetic restraint of arterial compliance. To date, studies in humans have examined sympathetic restraint of compliance via either reflexively or pharmacologically manipulating sympathetic vasoconstriction and measuring resultant changes in compliance. The extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) dynamically regulate arterial compliance in humans on a beat-by-beat basis remains unknown. Herein, we hypothesized that femoral arterial compliance would be transiently reduced following spontaneous bursts of MSNA. Further, we hypothesized that the magnitude of reduction in arterial compliance would be graded to the MSNA burst amplitude (index of net neural outflow). Beat-to-beat blood pressure (BP; Finometer), heart rate (ECG), MSNA (peroneal microneurography), and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured over 10-20 minutes of quiet supine rest in 27 young, healthy men (age: 22 ± 1 years, resting MSNA burst frequency: 11 ± 5 bursts/minute). Customized labview programs were used to time-align neural cardiovascular variables with ultrasound data sampled at 30Hz, enabling the quantification of arterial compliance on a beat-by-beat basis defined as the change in arterial cross-sectional area divided by the change in blood pressure over the cardiac cycle. Bursts of MSNA were tracked for 10 cardiac cycles and changes in arterial compliance were quantified using signal-averaging for all bursts, and subsequently, for bursts of MSNA when sub-classified based on amplitude into quartiles (Q1= smallest 25% of bursts, Q4= largest 25% of bursts). Reductions in arterial compliance were significantly greater following cardiac cycles with bursts of MSNA compared to cardiac cycles without bursts of MSNA (bursts: -5.1 ± 0.6% vs. non-bursts: -0.8 ± 0.2%, p&lt;0.001). Further, reductions in compliance appeared to be graded to MSNA burst amplitude (Q1: -6.5 ± 0.8%; Q4: -9.1 ± 1.3%, P=0.051). The latency (i.e., number of heartbeats) to nadir arterial compliance following bursts of MSNA was 4.2 ± 0.6 cardiac cycles. Collectively, these findings suggest that the sympathetic nervous system dynamically regulates femoral arterial compliance on a beat-to-beat basis. College of Nursing and Health Innovation, University of Texas at Arlington. 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.

Renal Oxidative Stress May Explain Sex Differences in Blood Pressure in Adult Offspring Exposed to an Impoverished Environment

Background: Nearly 40 million people experience poverty in the United States. Poverty is linked to adverse childhood experiences (ACEs) which affects about 64% of adults in the U.S. Previous studies indicate that those who experience ACEs are at a higher risk of developing hypertension (HTN) and cardiovascular diseases (CVDs) later in life, with a greater severity and earlier onset in males. The mechanisms behind the ACEs-attributed development of sex differences in HTN later in life is unknown. One plausible mechanism for this sex difference is increased oxidative stress. One rodent model to mimic poverty as an ACE is the limited bed and nesting (LBN) model. This model simulates an impoverished and low resource environment, as observed in poverty, in which the nesting material during weaning is reduced. We hypothesize that male offspring exposed to LBN will have elevated blood pressure and oxidative stress, while females will have no change in blood pressure and reduced oxidative stress. Methods: Pregnant Sprague Dawley rats gave birth naturally and weaned their offspring for 3 weeks. During the weaning period, on Days 2-9, the dams and their respective pups were divided into 2 groups: LBN and control (CON). After LBN treatment, all rats received normal bedding. After weaning, offspring were divided by sex and experimental status: LBN male (n=5), LBN female (n=5), CON male (n=6), and CON female (n=6). At 16-17 weeks, mean arterial pressure (MAP) was measured via carotid catheterization and the kidneys, brain, heart, and plasma were collected to measure antioxidant capacity via colorimetric biochemical assays. Results: LBN males had a significant increase (18 mmHg) in MAP compared to CON males (128.17±3.93 vs 110.72± 3.93 mmHg, P&gt;0.001), while female LBN and CON rodents displayed no differences. In males, there were no changes in antioxidant capacity in the brain, heart, and plasma. However, there was a significant 2-fold decrease in renal antioxidant capacity (233±14.0 vs 442±12.3 mM Trolox/mg protein, p&gt;0.0001). In females, there were no changes in the kidneys, heart, and brain antioxidant capacity. Conversely, LBN females showed a trending increase in plasma antioxidant capacity compared to CON (3.33±0.16 vs 2.53±0.35 mM Trolox/mg protein, p=0.053). Conclusion: Only males exposed to an impoverished environment during weaning have elevated blood pressure, while females do not. This difference in blood pressure may be explained by decreases in renal antioxidant capacity in males only. On the other hand, females may be protected from elevated blood pressure because they experience a slight increase in systemic antioxidant capacity. Future studies will examine the role of antioxidants in blood pressure regulation in the kidneys. This study is clinically relevant because ACEs affect a large percentage of the American population with about 17% of adults experiencing 4 or more ACEs, with minorities at a greater risk. Understanding the mechanisms on how ACEs contribute to HTN may alleviate some of the racial and ethnic disparities, along with the financial burden on the healthcare system to care for people with HTN and CVDs. Perhaps, organ and sex-specific antioxidant therapies may be used to alter, prevent, or reduce the development of HTN in adults that were exposed to ACEs, such as poverty during nursing and early childhood. This research was supported by start-up funds and the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)]. 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.

Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p&lt;0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p&lt;0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction. This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P). 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.

A Prebiotic Diet Increases Cardiovascular Adaptability Under Hypergravity-Induced Stress

Life in space presents significant challenges to mammalian physiology and the longer one is in space, the greater the impact. Three major stressors are present in space: 1) changes in gravitational environment, 2) psychological/physiological stress, and 3) constant low dose radiation. It is critical, therefore, to discover interventions that promote stress resilience. Dietary prebiotics selectively increase the relative abundances of probiotic bacterial species in the gut. We have previously reported that a diet enriched in galactooligosaccharide (GOS) and polydextrose (PDX) compared to control diet robustly elevates parabacteroides distasonis, clostridium leptum, and reduces the negative impact of acute and chronic stress. Interoceptors (e.g., baroreceptors) sense gravity-induced changes in blood pressure and cardiac function/structure. There is evidence that hypergravity disrupts autonomic and cardiovascular homeostasis and function. Cardiovascular homeostasis depends on a sympathetic and parasympathetic balance reflected in heart rate variability (HRV), a measure of cardiovascular stress. The following study was designed to test the hypothesis that GOS+PDX reduces the cardiovascular impacts of living in an altered gravitational environment. Adult female mice were housed in 1G or 3G and were fed GOS+PDX or a matched control diet for 4 weeks on the NASA Ames 1.22-meter radius centrifuge. We recorded electrocardiograms (ECG) in animals from all four groups immediately before, halfway through, and immediately after centrifugation. We analyzed HRV data using a Python-based Jupyter notebook and R. R was used to perform a 1F-LD-1F ANOVA with pair-wise comparisons to quantify changes in HRV longitudinally. Classic time domain based HRV metrics, standard deviation of the successive differences between adjacent R-R intervals and standard deviation of NN intervals, showed little change over time. Instead, frequency domain measures showed results were housing in 3G compared to 1G reliably changed Shannon entropy, Sample entropy, and low to high frequency ratio at each time-point. The changes across time reflected adaptation to hypergravity and a consequent reduction in HRV. Poincare plot analysis and low to high frequency ratio metrics showed divergent compensatory reactions between diets at 3G. Overall, 3G impacted HRV less in mice that were fed the prebiotic diet compared to the control diet. Further longitudinal studies with greater temporal resolution are needed to assess changes in HRV caused by gravitational changes. However, our data suggests the prebiotic diet significantly reduces 3G activation of sympathetic drive and increases parasympathetic drive, potentially reducing cardiovascular stress in animals exposed to high gravity. NASA grant 80NSSC19K1038 funded this project. 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.

Myeloid Specific Hypoxia Inducible Factor 1 Alpha contributes to Immune Metabolic Reprogramming in Human Salt Sensitive Hypertension

Salt-sensitivity of blood pressure (SSBP), acute changes in blood pressure that mirror dietary salt intake, is a major risk factor for cardiovascular disease independent of hypertension. We previously found that oxidative lipid protein modification via NADPH oxidase (NOX2) reactive oxygen species (ROS) production in antigen presenting cells (APCs) contributes to SSBP. Hypoxia Inducible Factor 1 Subunit Alpha (HIF1α) plays a role in metabolic reprogramming and maturation of dendritic cells but its role in the pathogenesis of SSBP is not known. I hypothesize that HIF1α expression specifically in APCs contributes to SSBP by promoting a switch to anaerobic energy production through glycolytic enzyme induction. To test this hypothesis, we performed both bulk and single cell transcriptomic analysis in circulating immune cells following both in vitro and in vivo salt-loading/depletion protocols to phenotype people for SSBP. We found that compared to normal (150 mMol/L), isolated monocytes from women (N =11) treated with high sodium (190 mMol/L) in vitro for 72 hours exhibited a marked increase in expression of HIF1α (16149 ± 6246.1 vs. 42233 ± 20836, p = 2.28E-05). This was associated with increased downstream expression of glycolytic enzymes LdhA (29600 ± 12391 vs. 55998 ± 17118, p = 0.013928), which catalyzes the conversion of pyruvate to lactate under anaerobic conditions, and PDK1 (1422.2 ± 880.80 vs. 2651.3 ± 1216.2, p = 0.0091) which attenuates the conversion of pyruvate to acetyl-CoA through inhibition of pyruvate dehydrogenase, stopping its entry to the citric acid cycle. Moreover monocyte-specific expression of PDK1 correlated with a decrease in systolic blood pressure from salt-loading to salt-depletion (r = 0.6753, p = 0.06608). Our data indicate that HIF1α may play a role the pathogenesis of SSBP by contributing to immune metabolic reprogramming. 1R03HL155041-01 (Kirabo, PI)1R01HL144941-01A1 (Kirabo, PI). 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.

Older versus Younger Females Matched for Body Composition Have Lower Sympathetic Transduction at Rest

BACKGROUND: Older female (OF) adults have the highest risk for hypertension and cardiovascular disease among any demographic in America. Therefore, there is a need to better understand the contributors to impaired blood pressure (BP) regulation in female aging. Bursts of spontaneously occurring muscle sympathetic nerve activity (MSNA) contribute to BP regulation on a beat-to-beat basis (i.e., sympathetic transduction). Previous work suggests that OF have attenuated resting sympathetic transduction but there is a need for additional work considering covariates that affect sympathetic transduction (e.g., body mass index (BMI) &amp; sodium intake). We tested the hypothesis that aging attenuates sympathetic transduction in OF (&gt;55 years) compared with young female (YF; 18-35 years) participants matched for body composition and pre-trial sodium intake. METHODS: We studied seven post-menopausal OF (65±6 years) and nine YF (24±4 years; tested in early follicular phase) participants with seated brachial BP &lt;140/90 mmHg after three days of specified sodium intake (target 2300mg/day). We measured mean BP (photoplethysmography) and MSNA (microneurography) during a 10-min rest period in the supine position. We also assessed BMI, body fat % (BF%; bioelectrical impedance), and habitual moderate-to-vigorous physical activity (MVPA) during ≥7 consecutive days using waist-worn accelerometers (ActiGraph). We compared the average change in BP for 10 cardiac cycles after an MSNA burst (i.e., signal-averaged sympathetic transduction) using mixed-effects models (group*time[repeated measure]). We compared other variables using unpaired, two-tailed t-tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data (i.e., failed Shapiro-Wilk test). We compared sodium intake, BMI, BF% and MVPA using equivalence testing. Significance was set to α&lt;0.05. RESULTS: Sodium intake, BMI, BF% and MVPA were equivalent between groups (p&gt;0.06). The following data are presented as OF vs. YF with mean ± SD or median[IQR]. Mean BP (97[22] vs. 77[5] mmHg, p=0.008) and MSNA burst frequency (35±6 vs. 13±4 bursts/min, p&lt;0.0001) were higher in OF. OF had lower mean BP changes following MSNA bursts (time: p&lt;0.0001, group: p=0.013, interaction: p=0.026) with pairwise differences among cardiac cycles 4-10 (post hoc p-values: p≤0.012). Moreover, peak increases in mean BP following MSNA bursts were lower in OF (Δ1.9±0.4 vs. 4.9±2.2 mmHg, p=0.003). CONCLUSION: We found that OF have attenuated sympathetic transduction to BP when compared to YF matched for body composition and sodium intake. This extends past work suggesting that female aging is associated with attenuated sympathetic transduction to BP. National Institutes of Health K01HL160772 (JCW), American Heart Association 23CDA1037938 (JCW), &amp; Florida State University Graduate School Legacy Fellowship, 2023 (CD). 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.

Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.

Load-Dependent Arterial Stiffness Mechanisms are Responsible for Increased Large Artery Stiffness Observed among Women with a History of Preeclampsia

Introduction: Preeclampsia is a pregnancy complication characterized by hypertension and multi-organ dysfunction and is a leading cause of maternal morbidity and mortality. Preeclampsia results in a two-four fold increased risk of developing hypertension and cardiovascular disease later in life. Large artery stiffness (LAS), a robust risk factor for hypertension and cardiovascular disease, and blood pressure (BP) are elevated after pregnancy in women with a history of preeclampsia (hxPE) and is associated with reduced cardiovagal baroreflex sensitivity (BRS). Whether elevated LAS in women with a hxPE is a consequence of structural remodeling of the arterial wall or the load applied to the arterial wall by the blood (i.e., BP) is unclear. Furthermore, it is unknown whether one or both LAS mechanisms are associated with differences in BRS. Therefore, we hypothesized that 1) structural- and load- dependent LAS would be elevated in women with a hxPE versus no hxPE postpartum controls, and 2) structural- and load- dependent LAS would be associated with BRS in women with hxPE.Methods: LAS was measured via carotid-femoral pulse wave velocity (aortic LAS), and carotid ultrasonography/tonometry (carotid LAS) among 115 women 1-5 years postpartum (age 34 ±4yrs; hxPE n=51; controls n=64). Participant-specific exponential models were used to standardize LAS measurements to a ‘reference’ BP (aortic: 90mmHg mean arterial pressure; carotid: BP 120/80mmHg) and used to calculate structural LAS. Load-dependent LAS was calculated as total minus structural LAS. Spontaneous cardiovagal BRS was measured using the sequence technique. Results: Systolic and diastolic BP were higher in women with hxPE compared with controls (all p&lt;0.001). Aortic, but not carotid, LAS was 0.57 m/s higher in women with hxPE compared with controls (p=0.025). Load-dependent LAS was 0.39 m/s (aortic) and 0.5 m/s (carotid) higher in women with hxPE (p&lt;0.001 for aortic and carotid), but no difference was observed for structural LAS measures (p&gt;0.14 for both). Women with hxPE had 4.13 ms/mmHg lower BRS compared to controls (p=0.042). In women with hxPE, BRS was negatively associated with both aortic and carotid LAS (r=-0.37, p=0.042 and r=-0.38, p=0.025, respectively), and aortic load-dependent LAS (r=-0.39, p=0.033), after adjusting for age and body mass index. Conclusion: Load-dependent LAS mechanisms explained the higher aortic and carotid LAS observed among women with a hxPE and was associated with lower BRS. Our findings suggest that changes in BP and cardiovagal BRS may underpin in part the higher LAS observed in women with a hxPE. Grant funding: American Heart Association 22TPA969732 (to GLP) and 18SCG34350001 (to MKS). 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.

Functional in vivo effects of an ENaC Na+ self inhibition-enhancing mutation

Background: Epithelial Na+ channel (ENaC)-mediated Na+ reabsorption in the distal nephron is a critical regulator of extracellular fluid volume and K+ homeostasis. Physiologic concentrations of extracellular Na+ reduce channel activity (open probability; PO) via an allosteric mechanism termed “Na+ self-inhibition,” which involves Na+ ions binding to specific sites in the channel’s extracellular domains. Recent studies have identified human ENaC mutations that alter the Na+ self-inhibition response when assayed in vitro. Such mutations may confer sensitivity or resistance to salt-induced blood pressure changes. Using CRISPR-Cas9 technology, we generated mice carrying a mutation previously shown to enhance Na+ self-inhibition (αH282R) to assess the effects on ENaC-dependent Na+ transport in vivo. We predicted that ENaC activity would be reduced in these mice, leading to enhanced sensitivity to Na+ deprivation or K+ loading, along with accompanying compensatory changes to overcome the predicted loss of function. Methods: We measured urinary electrolyte handling in wild type (WT) and αH282R mice maintained on normal, low Na+, or high K+ diets using metabolic cages. We assessed ENaC activity ex vivo using patch clamp and Ussing chamber methods. We also measured blood chemistry and aldosterone levels in WT and αH282R mice under the dietary conditions described above. Results: When maintained on a normal chow diet (0.3% NaCl), αH2832R mice expressed ENaCs in the distal nephron with reduced PO compared to WT littermates (0.026 vs. 0.067; p&lt;0.01), while ENaC subunit protein expression was unaltered. Amiloride-sensitive short-circuit currents were reduced in the distal colons of αH283R mice versus WT littermates (-12.6 vs. -3.9 μA/cm2; p&lt;0.01). Plasma aldosterone levels were also higher in αH283R versus WT mice on a control diet (610 vs 288 pg/mL; p=0.02), while no other differences in baseline blood chemistry were observed. When challenged with either dietary Na+ restriction (&lt;0.01% NaCl) or K+ loading (10% KCl), WT and αH283R mice responded similarly in terms of body weight maintenance, urinary Na+ and K+ excretion, and systemic electrolyte and metabolic parameters, with the exception of higher aldosterone levels in Na+-restricted αH282R mice compared to WT littermates (2,759 vs. 1271 pg/mL; p&lt;0.01). Conclusions: The αH282R mutation, which enhances Na+ self-inhibition, confers reduced ENaC activity in mice. However, this loss of function may be compensated by ENaC-independent Na+/K+ handling mechanisms and/or increased aldosterone signaling during adaptation to dietary salt stressors. P30DK079307, T32DK061296. 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.

Impact of seasonal blood pressure changes on visit-to-visit blood pressure variability and related cardiovascular outcomes.

Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk. In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model. SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints. Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations.

Carbon Dioxide as a Novel Blood Pressure Therapy for Neurogenic Orthostatic Hypotension

BACKGROUND: On standing, people with neurogenic orthostatic hypotension (nOH) experience plummeting blood pressure (&gt;20/10mmHg), crippling symptoms, and syncope. Current blood pressure therapies lack effcacy and have serious side effects. In healthy people, increased inspired CO2 increases blood pressure. This raises the tantalizing possibility that increased inspired CO2 may effectively treat nOH patients. OBJECTIVE: We aimed to understand if increased inspired CO2 can increase standing blood pressure in nOH. METHODS: Seventeen patients with nOH (F=5; 71±8 years) completed three randomized sit-to-stand tests with inspired CO2 maintained 0mmHg (0CO2), +5mmHg (+5CO2) or +10mmHg (+10CO2) relative to baseline. Respiratory and hemodynamics (blood pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance) were continuously measured. Data are reported as mean ± SD. The change (stand-sit) in respiratory and hemodynamics between 0mmHg, +5mmHg and +10mmHg were compared using a repeated measures ANOVA with a Bonferroni correction. RESULTS: Inspired CO2 caused a dose-dependent increase in standing blood pressure (0CO2:-43±25mmHg; +5CO2:-22±26mmHg; +10CO2:-4±30mmHg; p&lt;0.001). Blood pressure changes were predominantly facilitated by increased stroke volume (0CO2:-10±10mL; +5CO2:-5±10mL; +10CO2:0.1±10mL;p&lt;0.001) and cardiac output (0CO2:-0.2±0.6L/min; +5CO2:0.2±0.5L/min; +10CO2:0.7±0.5L/min; p&lt;0.001) as neither the changes in heart rate (p=0.2) nor systemic vascular resistance (p=0.6) were different across CO2 conditions. Breathing CO2 decreased the percentage of time that standing systolic blood pressure dropped ≥20mmHg (0CO2:75±35%; +5CO2:48±38%; +10CO2:32±37%; p&lt;0.001) and fewer patients met the blood pressure criteria for orthostatic hypotension (p=0.02). CONCLUSION: Our data indicates increased inspired CO2 can increase standing blood pressure in nOH patients by increasing stroke volume and cardiac output. CO2 may offer a novel pressor therapy for patients with nOH. This work was supported by a University of Calgary Seed Funding (S.R.R). J.R.B is supported by a Canadian Institutes of Health Research (CIHR) Fellowship, a Libin Cardiovascular Institute Post-Doctoral Fellowship in Women’s Cardiovascular Health, the Natural Sciences and Engineering Research Council of Canada (NSERC) Brain CREATE Program, and a Canadian Cardiovascular Society Fellowship. S.I.R. is supported by the NSERC Brain CREATE Program, an Alberta Graduate Excellence Scholarship, and an Alberta Strategy for Patient Oriented SUPPORT Unit scholarship. A.V.I is supported by a CIHR Fellowship and an Achievers in Medical Science Postdoctoral Fellowship. 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.