bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three main nitrate reservoirs in the mammalian body
Authors: Piknova Barbora , Park Ji Won , Tunau-Spencer Khalid , Schechter Alan 
Published: May 2023

Nitric oxide (NO) is a free radical with multiple functions in virtually all cells. In mammals, NO is generated by nitric oxide synthase from arginine and by reduction of nitrate/nitrite by tissue xanthine oxidoreductase (XOR) or microbiome. Previously, we reported in several mammalian species, including human, that skeletal muscle is a major nitrate reservoir in the body and that nitrate from this reservoir is systemically available and used to generate nitrite and NO. In our recent large animal study, we found that there are similar levels of nitrate stored in bone and skin. In our prior study, skeletal muscle showed a high level of nitrate at 57±39 nmol/g, relative to other tissues, such as liver and plasma at 15±5 nmol/g and 34±19 nmol/g, respectively. Here, we found that the average level of nitrate in the bone is 45±17 nmol/g and in the skin 41±19 nmol/g.Considering that the skeletal muscle, skin and skeleton are three largest organs in mammals, forming about 35-50%, 21% and 14% of body weight, respectively, these results highlight the importance of skeletal muscle as a main nitrate reservoir and the role of skin and bone as new auxiliary nitrate reservoirs. Along with skeletal muscle, the bones and skin likely play an important role in maintaining homeostasis of the nitrate-nitrite-nitric oxide pathway.Also, important from therapeutic point of view, all three organs are well responding to dietary nitrate interventions by increasing their respective nitrate levels, which leads to general increase of systemic and local NO availability and perhaps could be used as one of the ways to increase NO availability in some diseases. This work was supported by intramural NIDDK/NIH grant ZIA DK 025104-15 to Alan N. Schechter. 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.
Once Weekly 24 Hour Intermittent Fasting Improves Arterial Stiffness and Alters the Relative Abundance of Aortic T Cells in Obese Mice
Authors: Graham Elliot , Risk Briana , Zhang Mingyue , Weir Tiffany , Gentile Christopher 
Published: May 2023

BACKGROUND: Intermittent fasting (IF) is a popular dietary strategy that reduces body weight and improves cardiovascular health. However, questions remain whether IF can reduce arterial stiffness, an independent risk factor for cardiovascular disease that is associated with vascular inflammation. Thus, the primary purpose of this study was to determine whether IF reduces obesity-associated arterial stiffness and alters the abdominal aortic immune cell landscape. METHODS: Wild-type (WT) and obese (Ob) mice were randomized for a 10 week protocol to receive either ad libitum (Ad-Lib) control diet or a once weekly 24 hr fast (IF), yielding four groups: WT+Ad-Lib; WT+IF; Ob+Ad-Lib; and Ob+IF. Throughout the 10 week protocol, early- (weeks 1-2), mid- (weeks 5-6), and endpoint (weeks 9-10) indices of arterial stiffness were measured via arterial pulse wave velocity (aPWV). Following the intervention, mice were euthanized, and abdominal aortic immune cells were quantified via spectral flow cytometry. RESULTS: Fasting mitigated weight gain in Ob mice without affecting weekly food intake (change in body weight; Ob+Ad-Lib= 22.6 ± 0.8 g; Ob+IF= 20.0 ± 0.4 g; p=0.02). Earlypoint aPWV was similar between Ob+Ad-Lib and Ob+IF mice (Ob+Ad-Lib= 420.9 ± 15.6 cm/sec; Ob+IF= 450.7 ± 9.3 cm/sec; p=0.50), with aPWV in both Ob cohorts being significantly higher than in WT mice. At both the midpoint and endpoint, Ob+IF mice had reductions in aPWV that were significantly different from Ob+Ad Libs (midpoint=-36.5 ± 20.0 cm/sec, p= 0.02; endpoint= -21.6 ± 15.9 cm/sec, p=0.04). The number of aortic-resident lymphocytes was similar between the four groups. However, endpoint reductions in aPWV in Ob+IF mice were associated with reductions in the abdominal aortic CD4+ T cell: B cell ratio (r=0.50, p=0.04). An increase in the aortic CD4+ T cell: CD8+ T cell ratio was associated with reduced weight gain in Ob+IF mice (r=0.78, p<0.01). CONCLUSIONS: IF reduced weight gain and improved arterial stiffness in obese mice. Although the number of aortic-resident lymphocytes was similar between Ob+Ad-Lib and Ob+IF groups, reductions in arterial stiffness correlated to changes in the relative abundance of aortic CD4+ T cells in Ob+IF mice. This research was funded by NIH-HBLI (R01 HL144611) 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 Adolescent Ethanol Exposure on Lingual Taste Receptor Expression
Authors: Primeaux Stefany , Primeaux Jolie , Holmgren Eleanor , Wills Tiffany 
Published: May 2023

Adolescent alcohol use is prevalent in the U.S. and there is increasing evidence that neural and behavioral consequences of adolescent alcohol use may differentially alter the developing neural circuitry in males and females. Taste has been implicated in the preference for and intake of alcohol and alcohol exposure regulates taste perception. The detection of tastants (e.g. sweet, bitter, fat) is dependent on the density of lingual papillae and taste receptor expression. The goal of the current study was to examine the effects of adolescent ethanol exposure (AIE) on the density of fungiform papillae and lingual taste receptor expression from the circumvallate papillae (CV) in male and female C57/Bl6 mice. Mice (postnatal day (P)27) were exposed to intermittent ethanol vapor or volatilized water. The AIE protocol was run for two, 4-day cycles of 16h in-chamber sessions and 8h out-of-chamber sessions separated by 3 days from P27-P35. Ethanol vapor chambers were maintained to achieve blood alcohol concentrations ~ 200mg/dL. Mice were sacrificed 4-5 hours after their last ethanol exposure, and tongues were collected. Fungiform papillae were counted and density was determined in tongues stained with 0.5% methylene blue. Taste receptor expression for sweet (T1R2, T1R3), bitter (T2R138), and fat (CD36) tastes were assessed in the CV of the tongue using qPCR. Ethanol exposure significantly decreased fungiform papillae density and increased CD36 mRNA levels in the CV of male and female mice. A significant interaction between sex and ethanol exposure was detected for T2R138 and T1R2 mRNA levels in the CV. T2R138 mRNA was higher in control males compared to females, and AIE increased T2R138 mRNA levels in females, but not males. T1R2 mRNA level was increased by AIE in both male and female mice, however, there was a greater increase in females, compared to males. T1R3 mRNA levels did not differ between male and female mice and were not affected by AIE. Increased expression of fat and sweet taste receptors on the CV of male and female mice suggest that AIE may increase the sensitivity to and preference for foods and beverages that are high in fat and sugar. In females, AIE increased the expression of the bitter taste receptor, T2138, suggesting an increase in the sensitivity to and avoidance of bitter foods and beverages. Fungiform papillae density was decreased following AIE in males and females, which suggests an overall decrease in taste sensitivity following ethanol. Further understanding of ethanol’s effect on taste sensitivity is needed to better understand the long-term effects of adolescent ethanol exposure on food and beverage preferences and consumption patterns. NIHAA028011 T.W. 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.
Chronic Vagotomy Alters Glutamate Transmission in the Nucleus Tractus Solitarii (nTS)
Authors: Khodadadi Fateme , Hofmann Gabrielle , Kline David , Hasser Eileen 
Published: May 2023

The nTS is the first site of integration and processing of sensory afferent information and is one of the crucial brainstem nuclei involved in cardiorespiratory reflexes. This nucleus receives afferent information from many visceral structures in the thorax and abdomen via the peripheral branches of the vagus nerve. Vagal afferents release glutamate (Glu) which initiates signaling processes that leads to chemo- and baroreflex-mediated changes in sympathetic and phrenic nerve activity. Previous studies by us have shown that decreasing afferent input via unilateral vagotomy augmented nTS astrocyte complexity. Astrocytes contribute to regulation of Glu concentration by removing Glu from the synaptic cleft via excitatory amino acid transporters (EAATs). We hypothesized that vagotomy attenuates Glu signaling in the nTS due to increased Glu uptake by greater EAAT expression or function. Surgical transection or sham surgery of the right cervical vagus nerve caudal to the nodose ganglion was performed in male Sprague-Dawley rats. One week after surgery, mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA) were recorded in anesthetized and ventilated rats. Intact vagus nerves and the right phrenic nerve were acutely transected. Nanoinjections of Glu (30 nl, 1-10 mM) into the nTS decreased MAP, HR, SSNA and PhNA in both sham and vagotomy groups. Vagotomy blunted the HR, SSNA and PhrNA responses, indicating that Glu signaling was attenuated. To determine if increased EAAT function contributed to blunted Glu responses, the EAAT blocker TFB-TBOA (10nM, 60nl) was nanoinjected into the nTS. EAAT blockade mimicked the effect of Glu, producing similar depressor, bradycardic, and apneic responses in both groups. TBOA also enhanced the cardiorespiratory responses to Glu injection in both groups. EAAT blockade did not restore Glu responses in the vagotomy group compared to sham. Taken together, these data suggest that increased EAAT function did not account for the attenuated Glu signaling in the nTS. Further studies are needed to uncover the mechanisms by which vagotomy affects Glu signaling in the nTS. NIH R01 HL098602 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 pulmonary hypertension on diaphragm blood flow
Authors: Schulze Kiana , Horn Andrew , Weber Ramona , Ade Carl , Behnke Bradley , Poole David , Musch Timothy 
Published: May 2023

Pulmonary hypertension (PH) is a disease characterized by pulmonary vascular remodeling, respiratory muscle and cardiac impairments, and exercise intolerance. Specifically, impaired gas exchange increases work of the diaphragm; however, muscle fiber atrophy and compromised contractile function preclude the diaphragm from meeting the increased metabolic demand of chronic hyperventilation in PH. Given skeletal muscle contractile function is largely determined by adequate blood flow (Q̇), diaphragm contractile dysfunction may be predicated by an inability to match oxygen delivery with oxygen demand. Therefore, we hypothesized that diaphragmatic blood flow would be reduced in the diaphragm of PH rats. Additionally, we hypothesize that PH rats will demonstrate increased vascular resistance compared to healthy counterparts. Methods: Female Sprague-Dawley rats were randomly assigned to healthy (HC, n=5) or PH (n=5) groups. PH rats were administered monocrotaline (MCT; 50 mg/kg, i.p.) while HC rats were administered saline as a vehicle control. Disease progression was monitored via echocardiography. Fluorescent microspheres were used to determine regional and total blood flow (Q̇) and vascular resistance (VR) in the diaphragm at baseline and during 3 minutes of electrically-stimulated contractions. Results: All PH rats displayed morphometric and echocardiographic criteria for disease including right ventricular (RV) hypertrophy and a reduced pulmonary artery acceleration time (PA AT) compared to HC. In PH and HC rats, total Q̇ to the diaphragm increased and VR decreased during contractions. PH rats displayed a lower non-contracting baseline and contracting steady-state Q̇ to the whole diaphragm and the medial costal region (P<0.05) Medial costal VR was greater during contractions (0.90 ± 0.15 vs. 0.49 ± 0.06 mmHg/ml/min/100g; P=0.04) in the PH rats compared to HC. Conclusions: These findings support that bulk and regional diaphragm perfusion is reduced in PH, which suggests that PH comprises diaphragm vascular function and oxygen delivery, providing a putative mechanism for PH-induced diaphragm contractile dysfunction. Future studies will focus on investigating diaphragm arteriolar structural and functional properties to help resolve the mechanistic bases for these deficits and develop therapeutic countermeasures. This work was funded by the Sustained Momentum for Investigators with Laboratories Established (SMILE) Grant at Kansas State University College of Veterinary Medicine and the National Institute of Aging (1 R15 AG 078060). 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.
Reduced Hypoxic Ventilatory and Heart Rate Responses to Hypoxia in Post- versus Pre-menopausal Tibetan Women in Mustang, Nepal
Authors: Moya Esteban , Yu James , Craig Sienna , Buchanan Christina , Powell Frank , Beall Cynthia , Simonson Tatum 
Published: May 2023

Populations living at high altitudes exhibit distinct cardiovascular and ventilatory responses to hypoxia, which may result from exposure to the selective pressure of chronic hypoxia throughout hundreds of generations at high altitude. Compared to Andean highlanders and some acclimatized lowlanders, many Tibetans show an increased hypoxic ventilatory response (HVR) and lower hemoglobin concentration ([Hb]). While the effects of menopause on [Hb] have been well studied, its effects on HVR and heart rate responses to hypoxia (HHRR) in Tibetan women residing at high altitude have not been elucidated. We hypothesized that hypoxic ventilatory and heart rate responses to hypoxia decrease with menopausal status in Tibetan women, suggesting a change of adaptation during post-reproductive years in women. We measured minute ventilation (VI) and heart rate (HR) during room air and acute hypoxia in 376 Tibetan women (age range 46-86 years old) living in in Mustang, Nepal (>11,482ft / 3,500m) and compared responses between pre- and post-menopausal groups (mean ± SEM). Using a rebreathing system, we induced hypoxia to produce events of at least 10% desaturation (from 91 ± 0.2% to 78 ± 0.2%), expressed HVR and HRR as -ΔVI / ΔSpO2 and -ΔHR / ΔSpO2, respectively, and tested for associations between HVR and HHRR with age and [Hb]. HVR, HHRR, and [Hb] associated negatively with age in the post- but not pre-menopausal group. During hypoxia, post-menopausal women had lower VI (14.2 ± 0.2 L/min) and HR (80 ± 1 BPM) when compared (p<0.01) to pre-menopausal women (16.9 ± 0.4 L/min for VI and 85 ± 1 BPM for HR). VI was also lower in room air conditions (p<0.01) for post-menopausal (11.5 ± 0.1 L/min) versus pre-menopausal women (12.6 ± 0.2 L/min). HVR and HHRR was lower in post- (0.21 ± 0.01 L/%O2 and 0.65 ± 0.02 BPM/%O2 respectively) versus pre-menopausal women (HVR: 0.34 ± 0.03 L/%O2 and HHRR: 0.92 ± 0.05 BPM/%O2). Pre-menopausal women also exhibited negative correlations with HVR and HHRR with increasing [Hb]; however, these correlations were not significant in the post-menopausal group. A non-blunted HVR is a hallmark of adaptation in Tibetans, and physiological changes observed in Tibetan women during later life stages may result in a loss of such traits. These data suggest a hypothesis of menopause-related loss, or change, of adaptation to high-altitude hypoxia among middle-aged to elderly Tibetan women. Supported by NSF award 1831530 to CMB and NIH 1R01HL145470 to TSS. 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.
Influence of Various Legwear on Arterial Stiffness
Authors: Alhalimi Taha , Wang Tianyu , Tanaka Hirofumi 
Published: May 2023

Background: Carotid-femoral pulse wave velocity (cfPWV) has become a reference standard measure of arterial stiffness. This methodology requires a precise detection of pulse waves in the carotid and femoral arteries. A possible source of variability is the type of legwear when detecting femoral pulse waves since participants typically come in with their own legwear. In brachial blood pressure measurements, different types of fabric materials and thicknesses were founded to skew blood pressure readings. Accordingly, we investigated the effects of common legwear on cfPWV measured with both tonometery and oscillometry. We hypothesized that thicker and stiffer legwear would reduce both cfPWV. Methods: A total of 50 adults (36 women) varying widely in age (19-78 years old) and medical conditions were studied. Two devices that utilized a tonometric sensor (Omron VP-1000plus) and a cuff-based oscillometric sensor (Vicorder) to derive cfPWV were evaluated. The participants wore either khaki pants, sweatpants, athletic shorts, or medical shorts as a reference condition with an optional bare skin condition. These legwear were chosen as common legwear that participants wore when they were getting tested. All the legwear were provided to the participants with at least 10 minutes of rests between conditions. Results: As expected, the range of the means of cfPWV for the tonometric device was (659–672 cm/s) and (484–490 cm/s) for the oscillometric device. Both devices produced similar cfPWV values among different types of legwear as there were no systematic differences. Mean values of cfPWV measured with a bare skin condition did not differ significantly from all other conditions (20 - 27 cm/s) for the tonometric device and (2 - 5 cm/s) for the oscillometric device. Failure to obtain cfPWV using the tonometry were 13% for khaki, 6% for sweatpants, 3% for each of medical shorts and athletic shorts, and <1% for bare skin while the oscillometric device has a 0% failure rate among all conditions. Conclusion: Arterial stiffness as assessed by cfPWV was not affected by the type of legwear. Stiffer and thicker legwear increases the difficulty of detecting femoral pulses and increases the noise when measured using a tonometric sensor. When the oscillometric sensor was used, cfPWV was not affected by the type of legwear. Our present findings suggest that different legwear that participants wear may not be a concern when cfPWV is being assessed. There was no funding source for this study. 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.
Antiaging hormone Klotho derived from renal distal-convolution regulates calcium but not phosphate homeostasis
Authors: Pathare Ganesh , Kopper Klaudia , Trnjanin Adisa , Loffing-Cueni Dominique , Wengi Agnieszka , Loffing Johannes 
Published: May 2023

Soluble-Klotho (sKl) is the shed ectodomain of the transmembrane protein-Klotho (mKl) that exhibits pleiotropic actions, including lifespan extension, mineral metabolism, slowing-down kidney diseases and cardioprotection. The sKl is derived from the kidneys, but what type/s of renal cells secrete it is unknown. Secondly the respective roles of mKl versus sKl in regulating mineral metabolism is unclear due to the lack of appropriate in vivo models. Here, using scRNA-seq of renal distal-convolution (DC) cells, we found an unexpected pattern revealing that Klotho transcripts ( Kl) are moderately expressed in overall distal convoluted tubule (DCT), but highly enriched in the end of DCT and in connecting tubule (CNT). Immunohistochemistry further confirmed this pattern for mKl protein as well. Next, Kl was knocked-out only in renal DC to check if it affects sKl production. Interestingly, deleting Kl in the DCT and late-DCT+CNT in mice showed ~20% and ~80% reduction in sKl levels, respectively. Expectedly, knocking-out Kl along the entire DC in mice (Kl-KODC) abolished sKl levels. Furthermore, we found that compared to control mice, Kl-KODC mice exhibited reduced renal TRPV5-Ca2+ channel expression, profound calciuria, and loss of bone mineral density. The RNA-seq of automated-sorted DC cells from Kl-KODC mice revealed enhanced caveolae-mediated endocytosis of TRPV5. On the other hand, Kl-KODC mice had normal phosphate metabolism as confirmed by unchanged serum FGF23, serum phosphate, urinary phosphate excretion, and renal NaPi-IIa expression. Our findings reveal that a small population of renal DC cells accounts for the sKl levels. The lack of sKl may leads to disturbed Ca2+ homeostasis and bone loss without affecting phosphate balance in mice. 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.