bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial baroreflex control of heart rate in young and older adults and in patients with heart failure with preserved ejection fraction
Authors: Bunsawat Kanokwan , Holwerda Seth , Alpenglow Jeremy , Broxterman Ryan , Francisco Michael , Craig Jesse , Iacovelli Jarred , Weavil Joshua , Iannetta Danilo , Inglis Erin , Tuday Eric , Harrison Jonathan , Ma Christy , Ryan John , Wray D. Walter
Published: May 2023

Background: The arterial baroreflex (ABR) plays an important role in evoking appropriate cardiovascular adjustments in response to perturbations such as exercise. The ABR control of heart rate (HR) becomes attenuated with advancing age and in a variety of patient populations, but limited information is available in patients with heart failure with preserved ejection fraction (HFpEF). The present study tested the hypothesis that the ABR control of HR is attenuated to a greater extent in patients with HFpEF compared to older and young controls. Methods: Six patients with HFpEF (71±6 years; 35.3±6.6 kg/m2), 4 older controls (68±4 years; 25.1±3.4 kg/m2), and 7 young controls (27±4 years; 26.6±3.9 kg/m2) underwent sequential bolus infusions of sodium nitroprusside (50-100 μg) and phenylephrine (150 μg) (modified Oxford technique) to provoke acute hypotension (“BP falls”) and hypertension (“BP rises”), respectively. Cardiac baroreflex gain was quantified as the weighted linear regression slope between the R-R interval and systolic blood pressure (BP). Results: Compared to young controls (10.7±3.4 ms/mmHg), overall cardiac baroreflex gain was reduced in older controls (3.4±1.6 ms/mmHg) and patients with HFpEF (2.1±1.8 ms/mmHg) (p<0.05), with no difference between the older controls and patients with HFpEF (p=0.718). During BP falls, cardiac baroreflex gain was not different between groups (p=0.06), but was qualitatively lower in patients with HFpEF (0.6±1.5 ms/mmHg) compared to young (5.3±5.5 ms/mmHg) and older controls (5.2±1.9 ms/mmHg). During BP rises, cardiac baroreflex gain was not different between older controls (2.6±0.8 ms/mmHg) and patients with HFpEF (2.3±2.0 ms/mmHg) (p>0.05); however, responses in patients with HFpEF were attenuated compared to young controls 10.7±5.8 ms/mmHg) (p<0.05). Conclusion: These findings suggest an age-related attenuation in the overall ARB control of HR that does not appear to be further exacerbated in patients with HFpEF. However, patients with HFpEF may exhibit a selective attenuation in ABR-mediated tachycardia in response to acute reductions in BP that may pose an increased risk of hypotension and frank syncope.

This work was funded in part by the U.S. Department of Veterans Affairs (RX001311, to D.W.W.; IK2RX003670, to K.B.).

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.
Role of paraoxonase 3 (PON3) in regulating ENaC-mediated sodium transport in distal nephron
Authors: Shi Shujie , Mutchler Stephanie , Whelan Sarah Christine , Marciszyn Allison , Kleyman Thomas
Published: May 2023

PON3 is expressed in the aldosterone-sensitive distal nephron, where ENaC plays an essential role in maintaining Na+/K+ homeostasis in the kidney. The aims of our study were to determine the physiological roles of PON3 in renal Na+ and K+ handling. We hypothesize that PON3 functions as a molecular chaperone to regulate ENaC expressionand Na+ reabsorption in the kidney. We have obtained a Pon3 global knockout mouse model and examined the effect of PON3 on ENaC functional expression using several approaches, including biochemistry, immunohistochemistry, electrophysiology, and whole animal metabolic cage studies. Pon3 KO mice have normal kidney histology without evidence of inflammation or injury. At baseline, Pon3 KO mice have a significantly lower blood [K+] and higher blood [Na+] when compared to WT littermates. Amiloride-induced natriuresis was significantly greater in the KO mice, reflecting, in part, an upregulation in ENaC-dependent Na+reabsorption in the absence of the PON3. Immunoblotting of whole kidney lysates indicated that the total abundance of ENaC subunits was not altered in KO mice. Single channel recordings of ENaC in split-open tubules freshly isolated from WT or Pon3 KO mice kidneys demonstrated that open probability ( P O) was similar between the two groups of animals. However, the number of active channels per patch ( N) was significantly higher in Pon3 KO mice, resulting in a higher ENaC activity ( NP O) in the distal nephron segments of Pon3 KO mice. Consistent this notion, we found that ENaC γ subunit surface abundance was increased in mCCD cells when PON3 expression was knocked down by siRNA.Together, our data suggest that Pon3 KO mice have upregulated Na+ reabsorption and K+ secretion, likely a result of increased ENaC functional expression in the absence of PON3.

This study was funded by NIH grants R01 DK130901 (to SS), R01 DK111380 (to SS), R01 HL128053 (to TRK and SS), R01 HL147818 (to TRK), and P30 DK079307 (the Pittsburgh Center for Kidney Research). SMM was supported by T32 DK061296, T32 DK007052, and a grant from Relypsa.

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.
Underrepresentation of Women Participants in Exercise Science and Physiology Research is Associated with Authorship: A Historical Perspective
Authors: Linde Jessica , Klevenow Emilie , Atkinson Mira , Vosters Emma , Bueckers Elizabeth , Quinn Meagan , Hunter Sandra
Published: May 2023

The historically low representation of women as participants in exercise science and physiology research has led to a lack of understanding in the response of women to exercise and other therapeutic interventions. We hypothesize (1) the number of women authors and participants will increase over the last 30 years, and (2) a larger representation of women authors will be associated with an increase in the number of women participants. METHODS: Original research articles (n = 971) were analyzed from three journals (Journal of Applied Physiology, Medicine and Science in Sports and Exercise, and British Journal of Sports Medicine) in 1991 and 2021. These journals were chosen based on the following inclusion criteria: consistently ranked in the top 15 exercise science and physiology research journals, impact factor >3.5, ≥50 years of publications, and were accessible online. Articles were chosen from the following inclusion criteria: original research and not a review, included humans and not animals and did not solely use computational models. ANOVA and modified Pearson-Filon (ZPF) were used to statistically analyze the data. Data are reported as mean ± standard deviation. RESULTS: The number (percentage) of women authors was less in 1991 than 2021 (16 ± 22% vs. 31 ± 24%, p < 0.001) as well as the number of women participants (22 ± 32% vs. 36 ± 30%, p < 0.001). The percentage of women participants were less when the last author was a man compared to when the last author was a woman in 1991 (20 ± 30% vs. 34 ± 42%, p = 0.002) and in 2021 (32 ± 28% vs. 52 ± 33%, p < 0.001). Of all studies, 51% were authored by men only in 1991, which declined to 18% in 2021. In contrast, 1.8% in 1991 and 1.1% in 2021 were authored by women only. The correlation between authorship gender (number of women/total authors ratio) and participant gender (number of women/total participants ratio) grew between 1991 and 2021 (r = 0.27 vs. r = 0.42, p = 0.020). CONCLUSION: While the number of women authors and participants increased from 1991 to 2021, these numbers do not represent the current number of women in the population (~51%). Our data shows the historical underrepresentation of woman authors influences the low number of woman participants. Specifically, women authors included participants of both genders (men and women) at equitable numbers in exercise science and physiology research in 2021. The low representation of women as participants in exercise science and physiology research could be resolved by encouraging authors who are men to research equitable numbers of each gender.

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.
Pressure Regulation of Vascular L-type Calcium Channels
Authors: Mironova Galina , Baudel Miguel , Flores-Tamez Victor , Brett Suzanne , Navedo Manuel , Welsh Donald
Published: May 2023

Myogenic tone is dependent upon the activation of L-type Ca2+ channels and the rise in cytosolic [Ca2+]i. While L-type Ca2+ channel activation is often singularly linked to arterial depolarization, sparse evidence suggests that pressure itself may also enhance functional activity, through cooperative gating and trafficking. In this context, this study explored whether intravascular pressure indeed tune the myogenic response by enhancing the L-type Ca2+ channel trafficking and amplifying cooperative gating.Experimentation began in isolated smooth muscle cells (whole cell/single-channel patch clamp; immunohistochemistry; proximity ligation assay) and extended to intact arteries (pressure myography and Ca2+ measurements). Whole-cell electrophysiology revealed the ability of pressure stimuli to increase the L-type Ca2+ current, a response dependent on the intact cytoskeleton and enzymes tied to functional coupling (PKCα, AKAP150, PKA). Cell-attached electrophysiology confirmed whole-cell observations, registering increased coupling among L-type Ca2+ channels when cells were pressurized. Ensuing experiments on isolated arteries subsequently revealed linkage between intravascular pressure and enhanced L-type Ca2+ channel activity, independent of membrane depolarization.In closing, our results suggest there is more to L-type Ca2+ channel regulation than voltage gating and that pressure itself can enhance functional activity. Work continues to precisely define the pressure-sensitive signaling complexes within vascular smooth muscle.

Supported by the Canadian Institute for Health Research, National Institute of Health and the Rorabeck Chair in Vascular Biology and Neuroscience.

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.
Temporal and kinematics changes in jaw movement during feeding following chemoradiation to the rat submental muscles
Authors: King Suzanne , Scott Nathan , Smiley Brittany
Published: May 2023

Head and neck cancer patients treated with chemoradiation can develop radiation-induced dysphagia, which can significantly impact their quality of life. The submental muscles of the floor of mouth, such as the mylohyoid and geniohyoid, are at high risk for radiation-associated impairments in swallowing function. Prior work has shown that irradiating the submental muscles reduces the rate of tongue movement. During feeding, there is functional linkages between the jaw and tongue; therefore, an alteration in jaw movement could influence the position/shape of the tongue. The purpose of this study was to determine if chemoradiation treatment to the submental muscles alters jaw movement during eating. We hypothesized that the jaw speed and distance of movement during feeding would be modified following radiation treatment. Videofluoroscopic swallow study (VFSS) was performed on 18 Sprague-Dawley rats 1-month after chemoradiation, radiation alone or no treatment. Radiation was targeted to the submental muscles (12 fractions of 4Gy given three days a week for four weeks). Four cycles of 1mg/kg of cisplatin were administered concurrently with radiation. Rodents were provided peanut butter with 40% w/v barium and video recordings were taken at 250 frames per second with a customized c-arm. Jaw position along the xy axis was measured relative to the hard palate. Temporal and kinematic measures of the vertical movement of the jaw were analyzed. Significant decreases in jaw distance (p<0.03) and speed (p<0.02) traveled during licking were observed post treatment compared to untreated controls. The distance traveled during opening and closing phases of the jaw cycle were found to be decreased (both p<.03) following chemoradiation and radiation treatment. Results demonstrate that radiation-based treatments to the submental muscles impair jaw movement. The observed changes in jaw kinematics could potentially influence tongue position and shape during feeding.

The Ar-Hale Family Foundation; Jewish Heritage Fund for Excellence 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.
Gestational dependent responses to second hand smoke (SHS) in mouse pregnancies
Authors: Wendt Ryan , Stapley Brendan , Clark Evan , Curtis Katrina , Clarke Derek , Reynolds Paul , Arroyo Juan
Published: May 2023

Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights leading to the development of intrauterine growth restriction (IUGR) in mice. Hypertension and proteinuria are two important hallmarks of obstetric pathology leading to the development of preeclampsia (PE). In the present study, we wanted to determine the effects SHS exposure at two different important gestational points during mouse pregnancy. C57/Bl6 mice were exposed to SHS via a nose-only delivery system (Scireq) for 4 days (from 14.5 gestational day (dGA) to 17.5 dGA) or for 6 days (from 12.5 dGA to 17.5 dGA). At the time of necropsy (18.5 dGA) placental and fetal weights were recorded. Maternal blood pressure was determined with a tail occlusion cuff (Kent Scientific) and dip stick test for proteinuria was obtained. Treatment with SHS showed: 1) a significant decrease in placental weight (p<0.0001) and fetal weight (p<0.0002) following 4 days of exposure, 2) higher systolic (p<0.02) and diastolic (p<0.02) blood pressure following 6 days of exposure, and 3) increased proteinuria after 6 days of exposure. We conclude that detrimental effects of SHS coincides with the length of maternal exposure. We confirmed that 4 days of exposure resulted in metrics common to IUGR while 6 days of exposure more closely resembled PE pathology. These results could be beneficial in understanding the long-term effects of SHS exposure and the development of placental diseases.

NIH 1R15HD108743

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.
Identification of Molecular Markers of Diabetic Foot Ulcer Severity
Authors: Flores Mario , Flores Mario , Paniagua Karla
Published: May 2023

Diabetes prevalence estimates in South Texas exceeds national estimates and diagnosed cases are higher among Hispanic adults compared to their non-Hispanic white counterparts. San Antonio, a predominantly Hispanic city reports significantly higher annual rates of diabetic amputations compared to Texas. Late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk. In this study we investigate the use of a deep learning pipeline for single cell transcriptomics to identify key markers for Diabetic Foot Ulcer (DFU) severity and progression that can help prioritize individuals with high-risk of foot ulcer amputation. We observed substantial differences in cell types as well as transcripts of patients classified as non-DFU, DFU healers, DFU non-healers compared to healthy individuals. In particular cell sub-type composition show significant differences in DFU non-healers compared to non-DFU and DFU healers. As an indicator of immune defense, populations of T cells accounted for 5.26% in the non-healer group and decreased to 1.17% in the healer group. To obtain more insights into the molecular markers of severity, we developed a graph convolutional neural network (GCNN) model. We observed that the GCNN model reach a prediction accuracy of the severity of 90.32%. Overall, our study indicates significant differences in the gene expression profiles of inflammatory response and immune cells of non-healer patients. The identification of individuals with high risk of amputations is important to maintain the quality of life and thus has significant social-economic impact.

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.
Esophageal expression of Na+/H+ exchanger 2 and -3 (nhe2 and -3) gene transcripts in Atlantic salmon during smoltification and seawater acclimation
Authors: Richardson Sierra , Runiewicz Ellie , Bradley Serena , Hall Daniel , McCormick Stephen , Breves Jason
Published: May 2023

Atlantic salmon ( Salmo salar) undergo smoltification, a springtime transformation associated with the development of physiological, morphological, and behavioral traits that enable individuals to thrive in pelagic marine habitats. In particular, the capacity for salmon to maintain hydromineral balance in seawater is attained through the coordinated development of ion- and water-transporting processes in key organs such as the gill, kidney, and gastrointestinal tract. To combat dehydration, Atlantic salmon drink ambient seawater that is initially desalinated in the esophagus to enable subsequent solute-linked water absorption by the intestine. The molecular processes underlying esophageal desalination of imbibed seawater and their regulation during smoltification and following seawater exposure remain largely unresolved. The current study explored whether Na+/H+ exchangers in the esophagus may contribute to the removal of Na+ from luminal seawater. We first determined that both nhe2 and -3 were robustly expressed in the esophagus of smolts; nhe2 was also highly expressed in gill and stomach. Next, we sampled salmon undergoing smoltification and observed springtime elevations in branchial Na+/K+-ATPase activity, Na+/K+/2Cl- cotransporter 1 and cystic fibrosis transmembrane regulator 1 transcription that coincided with increased seawater tolerance. There were no parallel springtime changes in esophageal nhe2 or -3 expression; but nhe3 expression was enhanced in smolts after 2 days of seawater exposure. In a subsequent experiment, we observed elevated nhe2 and -3 expression in smolts that were long-term acclimated (2 weeks) to seawater versus freshwater. Collectively, our results indicate that Na+/H+ exchangers contribute to the desalination processes in the esophagus. The next challenge will be to determine whether essential “seawater-adapting hormones,” such as growth hormone and cortisol, regulate the expression of Na+/H+ exchangers in support of seawater acclimation. Supported by the National Science Foundation (IOS-1755131 to J.P.B.).

National Science Foundation [IOS-1755131]

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.
Lipoprotein lipase underlies the vascular anti-contractile effect of perivascular adipose tissue (PVAT)
Authors: Corley Scott , Costa Tiago , Wilson Emily , Waigi Emily , Wenceslau Camilla , McCarthy Cameron
Published: May 2023

Physiologically, perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature. This effect is mediated by the biosynthesis and liberation of a myriad of anti-contractile molecules (e.g., adipokines). However, this anti-contractile function generally is lost with aging and cardiovascular diseases such as hypertension and diabetes. Lipoprotein lipase (LPL) is an enzyme classically known for hydrolyzing triglycerides into free fatty acids and glycerol. However, it is unknown whether LPL underlies the anti-contractile effect of PVAT. Specifically, we hypothesized that by inhibiting lipoprotein lipase (LPL) activity with Atglistatin, we would abolish the anti-contractile effect of PVAT. To test this hypothesis, mesenteric resistance arteries (MRA), with and without PVAT, were isolated from 3-month-old male Wistar rats and mounted on a wire myograph. Phenylephrine concentration-response curves were performed with and without Atglistatin (10-5M). As expected, PVAT exerted a significant anti-contractile effect on phenylephrine-induced contraction [Emax (mN), -PVAT-vehicle: 18.1±3.0 vs. +PVAT-vehicle: 7.1±1.1, p<0.05]. Incubation of MRA with intact PVAT with Atglistatin significantly increased contraction [Emax (mN), +PVAT-vehicle: 7.1±1.1vs. +PVAT-Atglistatin: 22.6±4.2, p<0.05], suggesting that LPL is indeed important for the anti-contractile effect of PVAT. Crucially, no difference was observed with Atglistatin in MRA lacking PVAT [Emax (mN), -PVAT-vehicle: 18.1±3.0 vs. -PVAT-Atglistatin: 18.5±2.9, p>0.05], indicating that Atglistatin was not increasing contraction via non-PVAT-dependent mechanisms. Overall, these data suggest that LPL is an important mechanism mediating the anti-contractile effect of PVAT and that reduced LPL activity could be contributing to pro-contractile PVAT in aging and cardiovascular diseases.

NHLBI (R00HL151889), NIGMS (1P20GM103641 - Pilot Project), UofSC SOM (Startup funds)

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.
Deletion of PREX1 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 1) worsens salt sensitive hypertension and kidney damage in Dahl S rats
Authors: Liao Jenny , Liao Tang-Dong , Haque Mohammed , Ortiz Pablo
Published: May 2023

Prex1 (Phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1) is a Rac-specific guanine nucleotide exchanging factor and an integrator of signaling between Rac1 and protein kinase A (PKA). Both Rac1 and PKA are involved in pathways associated with salt sensitive hypertension. However, the roe of Prex1 in renal function and salt sensitive hypertension has not been studied. To investigate the role of Prex1 in salt sensitive hypertension. We used a Prex1 knockout (KO) rat on the Dahl salt sensitive genetic background generated by the RGERC at the Medical College of Wisconsin. Genotyping showed that the Prex1 gene was deleted. We studied the expression and localization of Prex1 in kidney sections using immunolabeling and confocal microscopy. Prex1 protein was mainly located in renal tubules, infiltrating inflammatory cells, and endothelial cells of large vessels. We then studied if deletion of Prex1 altered salt sensitivity of blood pressure. We found that both male and female WT Dahl S and Prex1 KO developed salt sensitivity after 2 weeks of 4% high salt diet. However, the increase in blood pressure was higher in male Prex1 KO Dahl S rats (Prex1 KO: 33± 7, vs male WT: 19± 2 mmHg, p<0.05). In females Prex1 KO, high salt increased BP by 31± 3 mmHg whereas the increase was lower in female WT Dahl S (17± 1 mmHg, p<0.05). Rats were placed in metabolic cages for urine collection. Male rats had increased albuminuria after high salt diet for 2 weeks that was not different between WT and Prex1 KO. Female rats had a smaller increase in albuminuria which was not different between WT and KO. Given the expression of Prex1 in inflammatory cells we quantified macrophage infiltration in the kidney after high salt diet. Male Prex1 KO rats had significantly higher macrophage infiltration compared to WT (WT: 141±10 vs Prex1 KO: 337± 18, p<0.05). Female Prex1 KO rats also had higher macrophage infiltration after high salt diet, but the total number of macrophages was lower than males (103 ± 7 female WT vs 208 ± 18 female Prex1 KO). We conclude that Prex1 protects against salt sensitive hypertension and inflammatory cell infiltration in Dahl salt sensitive rats such that its deletion worsens both phenotypes. Females Dahl S were somewhat protected against salt induced hypertension and this response was not worsened in Prex1 KO. Future experiments will study the role of Prex1 in renal NaCl transport.

NIDDK-R56DK131114

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.
Life science & interpreting students: an interdisciplinary healthcare role-playing activity
Authors: Halpin Patricia , Shaffer Laurie
Published: May 2023

Objective – Communication is essential to patient care. When serving Deaf patients, medical professionals who work with interpreters provide greater access to healthcare and wellness. Both the medical professional and the interpreter need training to develop the confidence and skills that support successful communication. This study aimed to introduce both Life Sciences and American Sign Language/English Interpreting undergraduate students to the experience of working together via role-play activities designed to promote effective communication with Deaf patients. Students from an Interpreting in the Healthcare Setting course were combined with students from an Endocrinology course to take part in this interdisciplinary assignment. Method – A group of three students per clinic completed each of the role play activities which were designed to simulate common interactions with medical professionals. The Life Science students enacted the role of the medical professional while one of the Interpreting students enacted the role of interpreter and the second enacted the role of a Deaf patient. Separate classrooms were designated as clinics where the role play was enacted. Clinics were designated as primary care intake, emergency department admissions, diabetes clinic and cardiac clinic. A mixed method approach was used to design both qualitative and quantitative questions on pre and post surveys distributed to 18 participants. The qualitative data was analyzed via collaborative review and categorized by theme. Quantitative Likert scale data was collected and analyzed to measure student preparedness, confidence and effectiveness of the activities. Results – The level of preparedness varied with each student and clinic type. All student participants from both courses reported increased confidence and ability when working with each other and with future Deaf patients. Conclusion – The study sought to create an authentic learning experience for undergraduate students who aspired to work in healthcare either as medical professionals or interpreters. By beginning such education earlier in students’ academic careers should result in more robust access to healthcare for Deaf patients. The model we created and evaluated can be used at all levels from community college through professional school to train Life Science students interested in health professions to provide equitable access to healthcare. For Interpreting students, the healthcare setting has a shortage of trained interpreters, and this model can provide them with the needed experience prior to working as interpreters in the healthcare setting.

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.
Arterial Baroreflex Control of Heart Rate in Patients with Chronic Kidney Disease
Authors: Li Sabrina , Jeong Jinhee , Sabino-Carvalho Jeann , DaCosta Dana , Park Jeanie
Published: May 2023

Chronic kidney disease (CKD) patients have greater blood pressure reactivity to acute cardiovascular stressors and a higher prevalence of hypertension; however, limited information is available regarding the potential role of impaired baroreflex control in non-dialysis CKD patients. The baroreflex plays a homeostatic role in beat-to-beat blood pressure (BP) regulation and impaired cardiac baroreflex sensitivity (cBRS) has been associated with increased blood pressure reactivity and cardiovascular events. However, previous studies in CKD have shown mixed results or have been confounded with co-morbid conditions such as hypertension. Therefore, the aim of the present study was to test the hypothesis that baroreflex control of heart rate (HR) is attenuated in patients with CKD compared to hypertensive controls. Additionally, we tested whether cardiovascular risk factors such as age, arterial stiffness, and BMI are associated with cBRS in patients with CKD. In 15 stage III-IV CKD patients [7 male/8 female, age: 60±10 yr, 14 Black/1 White, systolic/diastolic BP: 145.1±20/71.9 ± 10 mmHg, 100% hypertensive, BMI: 31±5 kg/m2] and 5 matched controls [5 male/0 female, age: 56 ± 4 yr, 5 Black/0 White, systolic/diastolic BP: 130.6± 24/69.0 ±15 mmHg, 100% hypertensive, BMI: 34±4 kg/m2], continuous beat-to-beat BP (finger photoplethysmography) and HR (electrocardiography) were recorded while resting supine for 5-minutes. We utilized the sequence technique in which the slopes of the systolic BP and RR interval relationships were calculated and averaged for a measure of cBRS. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) using tonometry. Systolic beat-to-beat BP (CKD 145.1±20 vs. CT 130.6± 24 mmHg, P = 0.184) and HR (CKD 64.2 ± 7 vs. CT 67.5 ± 6 beats/min, P = 0.352) were similar between groups. Likewise, no differences in spontaneous cBRSall (CKD 10.495 ± 5 vs. CT 8.800 ± 3 ms/mmHg, P = 0.487), cBRSup (CKD 9.138 ± 5 vs. CT 9.776 ± 3 ms/mmHg, P = 0.778) and cBRSdown (CKD 11.238 ± 6 vs. CT 8.218 ± 3 ms/mmHg, P = 0.267) were observed. No significant correlations were observed between cBRS with age, BMI, PWV, or eGFR. In summary, contrary to our hypothesis, our preliminary data suggest that CKD does not worsen cBRS compared to age- and co-morbidity-matched controls, but greater sample size is needed to support our results.

Funded by American Physiological Society, NIH R01HL135183, NIH R61 AT10457, and VA Merit I01CX001065.

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.
Spontaneous baroreflex control of sympathetic nerve activity and heart rate in young adults with major depressive disorder
Authors: Dominguez Cynthia , Darling Ashley , Skow Rachel , Young Benjamin , Saunders Erika , Fadel Paul , Greaney Jody
Published: May 2023

Blunted cardiac baroreflex sensitivity is evident in middle-aged adults with depression in remission and likely contributes to increased cardiovascular disease morbidity and mortality. In young adults with major depressive disorder (MDD), there is some evidence that sympathetic outflow at rest is elevated and graded in relation to depressive symptom severity; however, few studies have examined arterial baroreflex function in young adults with MDD. Here, we tested the hypotheses that spontaneous baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) would both be attenuated in young adults with symptomatic MDD (unmedicated) compared to healthy non-depressed adults (HA). Nine HA (22±3 yrs; 6 female) and 10 adults with symptomatic MDD of moderate severity [21±5 yrs; 8 female; 15±3 on the Patient Health Questionnaire-9 (possible score range: 0-27)] participated. MSNA (peroneal microneurography), HR (electrocardiogram), and beat-to-beat blood pressure (BP; finger photoplethysmography) were continuously measured during 10 min of supine rest. To determine spontaneous sympathetic baroreflex gain, weighted linear regression analyses between spontaneous changes in MSNA and diastolic BP (3 mmHg bins) were performed. To estimate spontaneous cardiac baroreflex gain, the relation between systolic BP and R-R interval was determined using the sequence technique. At rest, there were no group differences in MSNA burst incidence (28±10 HA vs. 21±10 bursts/100 heartbeats MDD; p=0.19), HR (62±9 HA vs. 69±11 bpm MDD; p=0.13), or mean arterial pressure (81±6 HA vs. 82±5 mmHg MDD; p=0.70). Sympathetic baroreflex gain was not different between HA and MDD (-3.4±0.8 HA vs. -3.0±1.5 bursts/100 heartbeats/mmHg MDD; p=0.53). There were also no differences in overall cardiac baroreflex gain between groups (24±11 HA vs. 19±6 ms/mmHg MDD; p=0.24). Likewise, there were no group differences in cardiac baroreflex gain when derived separately during either BP rises or BP falls (both p>0.05). These preliminary data demonstrate that spontaneous baroreflex control of both MSNA and HR are preserved in young adults with symptomatic MDD, suggesting that impairments in baroreflex function in adults with depression may only manifest later in the disease trajectory.

NIH R21MH123928 and R00 HL133414

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.
Sympathetic and blood pressure reactivity to acute stress in young adults with major depressive disorder: the influence of depressive symptomatology
Authors: Darling Ashley , Young Benjamin , Skow Rachel , Dominguez Cynthia , Saunders Erika , Fadel Paul , Greaney Jody
Published: May 2023

Major depressive disorder (MDD) is episodic in nature, highly recurrent, and associated with increased cardiovascular disease (CVD) risk. Sympathetic overactivation in response to acute stress may contribute to MDD-CVD comorbidity. However, few studies have investigated acute sympathetic stress reactivity in young adults with MDD or considered the potential influence of depressive symptom severity on these responses. We hypothesized that 1) acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) would be greater in young adults with MDD (unmedicated) compared to healthy non-depressed adults (HA) and 2) the magnitude of responsiveness would be graded in relation to symptom severity. Twenty-nine HA (22±5 yrs; 17 female) and 40 adults with MDD having mild-to-moderately severe depressive symptoms (23±6 yrs; 32 female) participated. Adults with MDD were also subclassified as having either low (l-MDD, n=25) or high symptom severity (h-MDD, n=15). MSNA (microneurography) and beat-to-beat BP (photoplethysmography) were measured at rest and during the cold pressor test (CPT) and the Stroop color word test (SCWT). There were no group differences in either resting MSNA (17±9 HA vs. 14±6 bursts/min MDD, p=0.39) or mean arterial pressure (MAP; 86±6 HA vs. 84±5 mmHg MDD, p=0.25). The CPT elicited increases in MSNA and MAP (both p<0.01), but the magnitude was not different between groups (MSNA: Δ24±12 HA vs. Δ19±9 bursts/min MDD, p=0.22; MAP: Δ24±8 HA vs. Δ23±9 mmHg MDD, p=0.45). The SCWT also elicited increases in MAP (p<0.01) that were not different between groups (Δ10±7 HA vs Δ10±6 mmHg MDD; p=0.76). Surprisingly, the SCWT failed to cause increases in MSNA (p>0.05), which also did not differ between groups (Δ-2±7 HA vs. Δ-2±8 bursts/min MDD, p=0.92). When further classifying adults with MDD into symptom severity subgroups, there likewise were no differences in MSNA reactivity to either acute stressor (both p>0.05). Interestingly, adults with h-MDD exhibited greater increases in MAP than adults with l-MDD during the CPT (Δ28±9 h-MDD vs. Δ20±8 mmHg l-MDD, p<0.01) but not during the SCWT (Δ9±4 h-MDD vs. Δ11±7 mmHg l-MDD, p=0.63). Contrary to our hypothesis, these data demonstrate that neither acute stress-induced sympathetic activation nor the ensuing increase in BP are exaggerated in young adults with MDD. However, the severity of active depressive symptomatology may influence BP reactivity to generalized stress stimuli, thereby influencing CVD risk profiles.

NIH R21MH123928 and R00 HL133414

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.
Glucose Induced Alterations in Fractal Fibrin Patterns
Authors: Snow Austin , Cordner Ryan
Published: May 2023

Arterial and venous thrombosis are major causes of morbidity and mortality in patients with diabetes. As hyperglycemia is known to enhance the risk of thrombosis, our work sought to evaluate the effects of hyperglycemia on fibrin polymerization patterns. Utilizing a novel method combining light microscopy images of blood clots and The Workflow of Matrix Biology Informatics, we were able to quantitatively evaluate alterations in fractal fibrin patterns. We found that increasing glucose concentrations correlated with decreased branch points, lacunarity, total length, and area. These changes suggest that glucose has a direct effect on fibrin polymerization, decreasing the total amount of polymerized fibrin, and altering the fractal patterns in a way that can be detected using light microscopy. Further work will be required to fully elucidate the impact of altered fibrin patterns on the development of arterial and venous thrombi in patients with diabetes.

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.
Alterations in mitochondrial function in endothelial and epithelial cells by plasma from E-cigarette users
Authors: Chitteti Ramamurthy , Juan Pablo Zuniga Hertz , Jorge A. Masso Silva , John Shin , Laura E. Crotty Alexander , Hemal H Patel , David M Roth
Published: May 2023

Background: Mitochondria play vital roles in cellular function and homeostasis. Inhalation of aerosols generated by E-cigarettes (E-Cig) may affect mitochondrial physiology. Data on risks of E-Cigs and vaping devices on mitochondria physiology remain incomplete. Our objective was to investigate novel effects of E-Cig plasma mediators on mitochondrial physiology in human endothelial (EA.hy 926) and lung epithelial cells (A549). Hypothesis: Plasma from E-Cig users will induce alterations in mitochondrial physiology. Methods: A longitudinal cohort study was conducted on subjects who used E-cigarettes (n=21) and 10 non-smoking, non-vaping controls. Inclusion criteria were active E-Cig use without known lung disease and with normal lung function, between the ages of 18-30 years. E-Cig use was confirmed with in-person interviews and plasma cotinine levels. Active E-Cig use was defined as use of >0.5-1 mL e-liquid/day or 3.5-7 mL/week for >6 months. Plasma was isolated and stored at -70°C. The metabolic stress effects of E-Cig plasma (1%, 1h conditioning) mediators were assessed in vitro on endothelial cells (8x104/well) and epithelial cells (5x104/well) using the Seahorse XF Energy phenotype Test. The mitochondrial copy number in E-Cig user plasma was estimated by digital droplet PCR. Membrane potentials and reactive oxygen species (ROS) were quantified by Cytation5. Results: E-Cig plasma altered the metabolic stress phenotype of mitochondria of EA.hy 926 and A549 cells. Metabolic stress was evidenced by increased oxygen consumption and glycolytic rates in both cell types. The mitochondria membrane potential and ROS levels significantly increased in E-Cig plasma subjected cells. Mitochondrial gene copy number levels were significantly increased in E-Cig user plasma suggesting mitochondrial stress in vivo. Conclusions: Plasma of E-cig users enhances maximal metabolic stress on human endothelial and lung cells in vitro and shows evidence for mitochondrial stress in vivo. These results may have important implications regarding the effects of E-Cig use on mitochondrial function and eventual public health recommendations.

T31IP1929 and R21 AG058174-01A1

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.
Role for insulin sensitivity in the cerebrovascular response to hyperinsulinemia in young adults
Authors: Gonsalves Anna , Shariffi Brian , Harper Jennifer , Manrique-Acevedo Camila , Padilla Jaume , Limberg Jacqueline
Published: May 2023

Objective: Cerebral blood flow is highly regulated and cerebrovascular responsiveness to vasodilatory stimuli is predictive of brain health. In preclinical animal models, insulin elicits cerebrovascular dilation and subsequent increases in cerebral blood flow. Contrary to this, preliminary data from our group in a large cohort of healthy humans indicate surrogate measures of cerebral blood flow remain at baseline levels during hyperinsulinemia – although responses were highly variable. In the peripheral circulation, insulin-stimulated vasodilation is closely associated with markers of insulin sensitivity (e.g., elevated fasting glucose, insulin, HOMA-IR); whether these associations translate to the cerebral circulation remains unclear. With this information in mind, we hypothesized the degree of insulin-mediated increases in cerebral blood flow would correlate with indices of peripheral insulin sensitivity.Methods: Middle cerebral artery blood velocity (MCAv) was measured with transcranial Doppler ultrasound in 17 adults (11M/6F, 28±2 yrs, 24±1 kg/m2) at baseline and following a 60-min hyperinsulinemic (40 mU/m2 body surface area/min), euglycemic infusion. Correlations between MCAv and indices of peripheral insulin sensitivity [i.e., fasting glucose, insulin, HOMA-IR, glucose infusion rate, weight, body mass index (BMI), age, physical activity] were determined. Results: Intravenous insulin infusion increased plasma insulin concentrations (6±1 to 49±3 μIU/mL, p<0.001) with blood glucose maintained (73±4 to 82±6 mg/dL, p=0.196). There was no net change in MCAv during hyperinsulinemia (60±4 to 60±4 cm/s, p=0.930). We observed negative associations between the change in MCAv during hyperinsulinemia (Δ=Insulin–Baseline) and both body weight (R=-0.49, p=0.047) and BMI (R=-0.50, p=0.040). No correlations between ΔMCAv and fasting glucose (p=0.435), insulin (p=0.733), HOMA-IR (p=0.960), age (p=0.132), physical activity (p=0.179), or glucose infusion rate (p=0.599) were observed. Conclusions: As previously shown in these participants, hyperinsulinemia in young adults elicits no net change in MCAv. Any increases in MCAv during hyperinsulinemia occur primarily in individuals with lower body weight and lower BMI. Future studies are needed to translate results to disease states (e.g., diabetes).

Margaret W. Mangel Faculty Research Catalyst Fund (JP, JKL), NIH HL137769 (JP), NIH HL130339 (JKL)

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.
Effects of temperature and water content on wet perception during the static touch of moist paper
Authors: Kato Issei , Masuda Yuta , Nagashima Kei
Published: May 2023

[Background] Wet perception plays an essential role in behavioral thermoregulation. It has been suggested that mechanical and thermal stimuli affect wet perception; however, the mechanism remains unclear. This study aimed to clarify the effects of water content and temperature on the wet perception of moist papers. [Methods] Twenty-seven healthy volunteers (14 males and 13 females, age 25 ± 5 years) participated in this study, which comprised two experimental trials. In Experiment 1, participants placed the index finger on 2 x 2 cm filter paper of 6 different water content (0.00, 3.75, 7.50, 11.25, 15.00, or 18.75 μg/cm2) for 15 s, of which temperature was controlled at 30ºC with Peltier apparatus. During the last 5 s of the stimulation period, participants were asked to report if they had wet perception or not. Each water content was presented five times, and the percentage rate of wet perception was calculated. In Experiment 2, participants placed the index finger on 2 x 2 cm filter paper of water content of 18.75 μg/cm2 for 15 s, of which temperature was controlled at either 20, 25, 30, 35, or 40°C with Peltier apparatus. During the last 5 s of the stimulation period, participants were asked to report the intensity of their thermal and wet sensations with a visual analog scale. Each temperature was presented five times. [Results] Experiment 1: The percentage rates of wet perception of 3.75, 7.50, 11.25, 15.00, and 18.75 μg/cm2 were significantly higher than that of 0.00 μg/cm2 ( p < 0.05). The percentage rates of wet perception of 11.25, 15.00, and 18.75 μg/cm2 were significantly greater than those of 3.75 μg/cm2 ( p < 0.01) and 7.5 μg/cm2 ( p < 0.005). Experiment 2: Thermal sensation of the stimuli of 25, 30, 35, and 40ºC was greater than that of the 20ºC stimulus ( p < 0.001). Wet perception of the stimulus of 20ºC was greater than that of 25, 30, 35, and 40ºC. Wet perception of the stimulus of 25ºC was higher than those of 30, 35, and 40ºC ( p < 0.05). [Discussion and Conclusions] The percentage rate of wet perception increased with the water content of the paper. Thus, participants could discriminate such small differences in the water content. The wet perception was augmented by stimulus temperature lower than 30ºC, while stimulus temperature above 30ºC did not show a clear relationship with the intensity of wet perception. The cold sensation may play an important role in modulating wet perception.

Research Fellow of Japan Society for the Promotion of Science and Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research A 19H01128.

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.