bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic exercise training attenuates the peak blood pressure response to exercise in chronic kidney disease
Authors: Mehrer Justin , Stock Joesph , Kirkman Danielle , Edwards David 
Published: May 2023

Chronic kidney disease (CKD) is an expanding public health problem. Patients with CKD have reduced exercise tolerance and are at a high risk for cardiovascular disease and events. Previous work has demonstrated that an exaggerated blood pressure response to exercise occurs in these patients which may contribute to their poor exercise capacity and increased cardiovascular risk. The purpose of this study was to test the hypothesis that 12 weeks of aerobic exercise training would attenuate the peak blood pressure response to exercise in patients with CKD. METHODS: Twenty-eight patients with stage 3 and 4 CKD (mean±SD: estimated glomerular filtration rate 43 ± 12 ml/min/1.73 m2) were randomly allocated to an exercise training (EX) or control (CON) group. EX consisted of 12 weeks of supervised aerobic exercise 3 times per week. Exercise duration and intensity progressively increased to 45 minutes at 65% to 85% heart rate reserve. CON received routine care. Cardiopulmonary exercise testing was performed on a cycle ergometer at baseline and following 12 weeks. Exercise intensity increased by 15W every minute and automated breath-by-breath gas analysis averaged over 10 seconds intervals was acquired throughout the protocol. Blood pressure (Tango M2, SunTech, NC) was recorded at rest and every 2 min throughout exercise and recovery. RESULTS: Twelve weeks of EX increased both VO2peak (p<0.01) and exercise duration (p<0.01). At 12 weeks, peak systolic blood pressure was not different from baseline in the EX (207 ± 32 vs 206 ± 35 mmHg; p=0.86) or CON groups (192 ± 39 vs 194 ± 39 mmHg; p=0.85). Exercise training significantly reduced peak diastolic blood pressure (91 ± 14 vs 81 ± 14; p = 0.002) whereas this was unchanged in the CON group (82 ± 15 vs 84 ± 15 mmHg; p=0.66). CONCLUSION: Twelve weeks of aerobic exercise training improved exercise capacity and attenuated peak diastolic blood pressure during exercise in patients with stage 3 & 4 CKD. The reduced blood pressure reactivity observed following exercise training in CKD may reduce cardiovascular risk and requires further investigation. Funding source: National Institutes of Health, National Heart Lung and Blood Institute grant R01HL113514 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.
Early Spinal Microglial and Non-microglial Cell Responses to Systemic LPS in Rats
Authors: Nikodemova Maria , Berschel Mackenzie , Michaelson Alysha , Parikh Komal , Mitchell Gordon 
Published: May 2023

Systemic inflammation associated with a wide range of clinical disorders elicits neuroinflammation in the CNS, exacerbating neurodegeneration or traumatic/ischemic injuries. Neuroinflammation also impairs important forms of neuroplasticity associated with cognitive and motor learning. Several mechanisms propagate systemic inflammation into the CNS, although important details are not yet understood. Reports suggest propagation via vagal pro—inflammatory sensory afferent neurons, and/or cytokines crossing the blood-brain barrier. Microglia are the resident CNS immune cells, and are key contributors to CNS neuroinflammation, producing cytokines, chemokines, NO and ROS. Important contributions are also known from other CNS cells ( e.g. astrocytes, pericytes and neurons). Here, we investigated CNS responses to systemic inflammation induced by systemic LPS injection (1mg/kg, i.p.) in 3 months old Sprague-Dawley rats to test an early stage in the neuroinflammatory process. Three hours post-LPS injection, rats were perfused with PBS followed by microglia isolation from cortex and cervical spinal cord via immunomagnetic separation; the microglia-free fraction (neurons, astrocytes, pericytes, and other cells) was also collected for analysis. The efficacy of microglial isolation was verified by flow cytometry, and both microglial and non-microglial mRNAs were analyzed via qRT-PCR. CD200 and CX3CL1 (fractalkine) are two proteins expressed exclusively by neurons that mediate neuron-microglial communication by interacting with microglial receptors. Post-LPS, both CD200 and CX3CL1 increased 2.5 and 8 fold, respectively. Colony stimulating factor 1 (CSF-1), a protein produced by astrocytes and oligodendrocytes that is crucial for microglial survival, increased 5-fold. Surprisingly, inflammatory cytokines IL6, IL1β, CCL2, iNOS and TNFα were significantly elevated in non-microglial cells, but only IL6 and iNOS were increased in microglia 3 hours post-LPS. Thus, non-microglial cell responses to systemic inflammation appear to occur prior to full microglial activation. We hypothesize that peripheral pro-inflammatory signals propagate into CNS via pericytes and/or astrocytes that are in close contact with blood vessels. Further studies are needed to identify specific cellular sources of pro-inflammatory cytokines. Since CD200 prevents excessive inflammation in peripheral tissues, we also hypothesize that neuronal CD200 upregulation limits microglial immune responses, preventing inappropriate over-activation. Supported by: R01 HL149800 & HL147554 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.
Sex differences in the erythropoietin response to hot tub treatment and carbon monoxide inhalation
Authors: DiMarco Kaitlyn , Chapman Christopher , Matsell Emma , Weiser Natasha , Grivette Margaret , Lucernoni Katie , Halliwill John , Lovering Andrew , Minson Christopher 
Published: May 2023

The kidney increases erythropoietin (EPO) when oxygen delivery is reduced, and when reductions in oxygen delivery are sustained, increased EPO results in increased red blood cell (RBC) production. More recently, carbon monoxide (CO) and heat have been used chronically to increase RBC production and therefore hemoglobin (Hb) mass. However, studies examining the acute effects of these interventions are limited, and no studies have examined these interventions in women. The purpose of this study was to examine the effects of CO inhalation and heat treatment alone and in combination on circulating EPO and determine if there are sex differences in these responses. 11 healthy subjects completed the study (6 women). Baseline blood was drawn to measure iron, ferritin, and transferrin concentrations. Hb mass was measured via the 10-minute CO-rebreathe method. Subjects completed three interventions – CO inhalation (carboxyhemoglobin 13.01±2.5%) hot tub immersion (40 degrees C for 45 minutes), and combined CO and hot tub – in a randomized crossover design. Renal blood velocity (RBV) was measured via ultrasound during all interventions. Venous blood was drawn at baseline and every hour for 6 hours post-intervention for measurements of EPO. All interventions reduced renal oxygen delivery (Δ47.5±21mL O2/min), and there were no sex differences in the reduction in oxygen delivery. All three treatments similarly increased EPO from baseline to peak concentration (Δ4.94±5.6mIU/mL). Women had a significantly greater increase in EPO than men to all three interventions (Δwomen 8.22±5.6mIU/mL; Δmen 1±2.06mIU/mL). The degree of EPO increase on all three days negatively correlated with Hb mass (R2=0.64) and positively correlated with transferrin (R2=0.73). Women may respond better to these interventions aimed to increase EPO, but the degree of responsiveness may depend on baseline Hb mass as well as transferrin concentrations. Wu-Tsai Human Performance Alliance at Oregon 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.
Skeletal muscle reactive hyperemia is dependent on the deoxygenation stimulus in young healthy humans
Authors: Durbin William , Kirby Brett , Crecelius Anne 
Published: May 2023

Reactive hyperemia tests create mismatches in oxygen (O2) delivery and demand by occluding blood flow and O2 delivery in the face of stable quiescent skeletal muscle O2 demand. We tested the hypothesis that skeletal muscle reactive hyperemia is dependent on the specific deoxygenation stimulus. We hypothesized that the magnitude of deoxygenation (Δ=nadir-baseline) would correlate with the magnitude of the reactive hyperemic response (Δ=peak-baseline), whereas the total deoxygenation (O2 debt, calculated as the total area under the curve of deoxygenation, below baseline) would correlate with the total reactive hyperemic response (area under the reactive hyperemia curve, above baseline). In six (3M:3F) young healthy adults, we continuously measured forearm blood flow using doppler ultrasound on the brachial artery and muscle O2 saturation via near-infrared spectroscopy (MOXY) during three lengthening occlusion timed-reactive hyperemia tests (1, 5, or 10 minutes in duration). The magnitude of deoxygenation was significantly (P<0.05 via paired t-test) less during 1 min occlusion (-13±1.6%) compared to either 5 min occlusion (-67±14%; P=0.0015) or 10 min occlusion (-74±10%; P=0.0004), but 5 min vs 10 min occlusion were not different (P=0.40). Similarly, the magnitude of the RH was greater in both the 10 min occlusion (329±102 ml/min; P=0.0004) and 5 min occlusion (295±123 ml/min; P=0.005) vs 1 min occlusion (131±69 ml/min; P<0.0001), but were not different from one another (P=0.11). However, the total deoxygenation increased progressively from 1 min (-335±51 units), to 5 min (-10732±2209 units), to 10 min (-32357±5053 units; all P<0.01) as did the total reactive hyperemic response (1 min:1326±927 ml; 5 min:7865±4055 ml; 10 min:17447±9698 ml; P<0.01). These results suggest that two distinct deoxygenation factors, the absolute magnitude of and the total mismatch between O2 supply and demand, may guide human skeletal muscle's reactive hyperemic response profile. The increased duration in a deoxygenated state observed in the 10 min occlusion leads to a greater overall reactive hyperemia response, potentially mediated by increased muscle metabolite production and greater bioavailability of vasoactive products mediated by the fully deoxygenated erythrocytes. 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.
No effect of nitric oxide on pulmonary pressure response to SCUBA diving
Authors: DiMarco Kaitlyn , Futral Eben , Drvis Ivan , Glavicic Igor , Lord Rachel , Banic Ivana , Dujic Zeljko , Lovering Andrew 
Published: May 2023

Some SCUBA diving time and depth profiles have been shown to increase pulmonary artery systolic pressure (PASP) post-dive. SCUBA diving while breathing compressed air results in a hyperoxic fraction of inspired oxygen and SCUBA divers are not hypoxic following a dive, so hypoxic pulmonary vasoconstriction is not responsible for the observed increase in PASP. In addition, no studies to date have examined whether the increased PASP is due to vasoconstriction or increased cardiac output (Q) following the dive. The purpose of this study was to examine whether nitric oxide availability post-dive is associated with the increased pulmonary pressure following SCUBA diving. 26 subjects completed the study (6 female). Subjects completed two dives (18 meters of sea water, 47 minute bottom time) on back-to-back days. Subjects were given sildenafil or placebo in a randomized and balanced crossover design upon resurfacing from their dive. Cardiac ultrasound for measurements of PASP and Q were done before diving and 1 hour after drug ingestion upon resurfacing. Total pulmonary resistance (TPR) was calculated as PASP/Q. PASP (p=0.0186) and TPR (p=0.0156), but not Q (p=0.779), increased on day 1 in the sildenafil group only. Irrespective of drug treatment, PASP was significantly higher by 2.58 mmHg at pre-dive on day 2 compared to pre-dive day 1 (p = 0.031). The increase in pulmonary pressure with SCUBA is likely independent of nitric oxide bioavailability. In addition, pulmonary pressure may remain mildly elevated for up to 24 hours after a SCUBA dive at 18m for 47 minutes. PADI Foundation Diving Physiology Grant (2021 - 2022), Title: Is SCUBA diving-induced pulmonary hypertension related to blood flow through patent foramen ovale and inflammation? AT Lovering (PI), Zeljko Dujic (Co-I); Fulbright Scholars Program (2019 & 2022), Title: Investigating the role of intrapulmonary and intracardiac shunts in mediating breath-hold diving-induced and SCUBA diving-induced pulmonary hypertension. A.T. Lovering (PI); University of Oregon College of Arts & Sciences International Research Travel Grant (2022), AT Lovering (PI); Global Oregon Faculty Research Travel program (2022), AT Lovering (PI) 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.
Paradoxically reduced pulmonary vascular resistance and abnormal vascular remodeling in the obese spontaneously hypertensive heart failure ZSF1 rats
Authors: Buncha Vadym , Bagi Zsolt 
Published: May 2023

Pulmonary arterial dysfunction and remodeling often develop secondary to left heart disease and systemic hypertension. Excessive body weight is a well-established independent risk factor for the development of cardiovascular disease. However, data have emerged that for heart failure associated pulmonary complications obesity displays a lower long-term mortality. The impact of obesity on hypertension-related heart failure in affecting pulmonary vascular changes is incompletely understood. Here, we examined pulmonary vascular resistance and pulmonary artery function and remodeling in obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. 20-week-old male obese ZSF1 rats display increased left ventricle (LV) hypertrophy and diastolic dysfunction, when compared to age-matched lean spontaneously hypertensive heart failure (SHHR). Pulmonary vascular resistance, pulmonary arterial function and vascular wall remodeling were examined in isolated and perfused, ventilated lung preparations and isolated small pulmonary artery pressure and wire myography, respectively. We found that the pulmonary vascular resistance (normalized to lung weight) was significantly reduced in obese ZSF1 rats compared to SHHR (ZSF1: 0.2±0.02 mmHg·mL-1·min·g-1 vs SHHR: 0.29±0.018 mmHg·mL-1·min·g-1, p=0.01). In isolated pulmonary arteries the acetylcholine-induced relaxation was maintained, whereas the nitric oxide donor, sodium nitroprusside-induced relaxation was reduced in obese ZSF1 rats (SNP -log(IC50) ZSF1: 4.185±0.166 vs SHHR: 4.96±0.136, p=0.005). The wall thickness and wall-to-lumen ratio of pulmonary arteries were higher in the obese ZSF1 rats when compared to SHHR. Collectively, we found that obesity is associated with a reduced pulmonary vascular resistance and abnormal pulmonary artery remodeling in rats with systemic hypertension and diastolic heart failure, which may have implications in the clinically observed obesity paradox. 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.
Eardrum tuning of the túngara frog
Authors: Wong Robert , Gridi-Papp Marcos , Paduano Mary , Tang Justine , Lee Betty , Morozumi Mark , Vo Trisha 
Published: May 2023

Frogs rely heavily on acoustic communication to mediate their social interactions in reproduction. The frequency tuning of their ears tends to match that of the calls promoting effective communication. In small species such as the túngara frog, extratympanic pathways involving the body wall and lungs can also be relevant routes of sound reception. Electrophysiological recordings from the midbrain of the túngara frog indicate the greatest auditory sensitivity around 1-1.1 kHz and elevated around 2 kHz. This tuning is a close match to the peaks in their calls (around 1000 Hz for whine and 2400 Hz for chuck) and reaches surprisingly low frequencies considering their small body size, raising the question of how is the low peak received by the auditory system. We characterized the tuning of the eardrums and body walls using Doppler laser vibrometry while stimulating anesthetized subjects with a series of pure tones ranging from 0.2 to 18 kHz and having an amplitude of 80 dB at the subject. Each data set was collected in 5 repetitions with the auditory stimulus and 5 repetitions without the auditory stimulus as a control. The eardrum was expected to be the main auditory pathway and the body wall was a secondary but relevant pathway potentially tunned to lower frequencies. Both the eardrum and the body wall showed significant vibration response to the stimuli with the highest sensitivity at 2-3 kHz. This matches the auditory tuning of other small frogs but it is mismatched with the electrophysiological peaks at low frequencies recorded in previous studies. Our results indicate that either there is a significant loss (~ 50 dB) of the mating call's energy in the tungara frog's auditory system or that the low frequencies (< 1.5 kHz) are received through an undescribed mechanism. Indirectly funded by an SAAG Grant. 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.
Differential regulation of RhoA by TAS2R signaling in airway smooth muscle relaxation
Authors: Conaway Stanley , Hernandez-Lara Miguel , Deshpande Deepak 
Published: May 2023

RATIONALE: Airway smooth muscle (ASM) hypercontraction and hyperresponsiveness are hallmark features of bronchoconstrictive disorders, which affect over 300 million people worldwide. Furthermore, the current standard of care, β-(adrenergic) agonists, lose their effectiveness for over 50% of patients that use them. Previous work in our lab resulted in the discovery of the expression of type 2 taste receptors (TAS2Rs) in human ASM. Interestingly, TAS2R agonists were found to elicit relaxation in a phospholipase C beta (PLCβ)-dependent manner. Furthermore, recent phosphoproteomics data from our group suggest that RhoA, an important contractile-related effector of PLCβ, is differentially regulated by TAS2R and β-agonists. Therefore, the goal of this study was to validate these findings and elucidate differences in the effects of multiple GPCR pathways on RhoA activity and ASM relaxation. METHODS: We determined the level of RhoA activity in human ASM cells (hASM) using the Rhotekin protein construct, which contains a Rho-binding domain with a high affinity for active RhoA. Additionally, we utilized lentiviral particles containing a single chain fluorescence resonance energy transfer (FRET) biosensor construct (RhoA2G) with a Rho-binding domain specific for active RhoA. Healthy hASMs were transduced with lentivirus and RhoA activity was monitored using fluorescent confocal microscopy. Cells were treated with TAS2R (chloroquine or flufenamic acid) or β (isoproterenol) agonists alone or in conjunction with the Gq agonist histamine to study the effects of these relaxant ligands on histamine-mediated RhoA activation. RESULTS: Our RhoA pulldown data using the Rhotekin construct showed that isoproterenol partially ablated histamine-mediated RhoA activation compared to the complete ablation of the signal by chloroquine (300 μM). Additionally, we observed complete ablation of histamine-mediated RhoA2G activity by isoproterenol while chloroquine and flufenamic acid evoked a reduction of histamine-mediated activity to below the observed baseline. This further validates our phosphoproteomics findings which suggest that histamine-mediated phosphorylation of ARHGEF12, a highly expressed RhoA activator, is partially attenuated by isoproterenol but fully attenuated by chloroquine (300 μM). Further, the RhoA FRET biosensor was useful in assessing the activation kinetics of RhoA in hASMs in real time. CONCLUSION: RhoA is an important contractile-related effector that is regulated differentially by isoproterenol and TAS2R agonists to evoke ASM relaxation. The studies in this abstract are funded by the NHLBI Diversity Supplement for the NIH grant R01-HL137030 (D.A. Deshpande) 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.