bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of carotid body chemosensitivity in lean and obese mice: Implication for obesity induced hypertension
Authors: Roy Arijit , Williams Noah , Polotsky Vsevolod 
Published: May 2024

Obesity is associated with increased circulating level of the hormone leptin. Previously we have shown in mice that, leptin induces hypertension acting on transient receptor potential melastatin 7 (Trpm7) channels in the carotid body (CB), a multi-modal peripheral chemoreceptor organ that controls breathing and drives sympathetic tone. Further, in mice leptin augments hypoxic ventilatory response which is abolished by CB denervation. This suggests a potential involvement of CB chemosensitivity. However, no comparative study of CB chemosensory responses has been conducted in lean and obese mice to support this notion. Based on these premises, we hypothesize that obese mice should have higher leptin induced CB chemosensory responses during normoxia and hypoxia compared to lean mice, and Trpm7 receptor antagonist should abolish/reduce these responses. To prove this, we measured afferent carotid sinus nerve (CSN) activity, using a novel ex vivo perfused mouse (male) CB preparation from lean (b.w.; 35 ± 0.5 gm) and diet induced obese (DIO) mice (b.w.; 53 ± 1.5gm) with C57BL/6J background. We found that compared to lean mice; (a) CSN response to hypoxia (PO2 =60 Torr) was 50% more in obese mice, (b) in presence of leptin (50nM), CSN responses to normoxia (PO2=100Torr) and hypoxia were augmented 50% and 150% more respectively in obese mice. Finally, leptin induced increase in CSN responses were partially reduced by Trpm7 antagonist FTY720 (3μM) in obese compared to lean mice. In conclusion, CB chemosensitivity is enhanced in obese compared to lean mice and CB Trpm7 channel could be a therapeutic target for obesity related hypertension. Grant support: NIH R01 HL1331000. 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.
Dietary Sodium Density and Blood Pressure in Athletes and Non-Athletes in Young Adulthood and Midlife
Authors: Irwin Jessica M. , Krieger Kristina , Mirkes Lindsey M. , Edwards David G. , Capin Jacob J. , Lennon Shannon L. 
Published: May 2024

Current recommendations for the general population limit sodium intake to 2,300 mg/d, however meeting these recommendations may be challenging for athletes, who have greater energy needs. Athletes with greater energy needs are recommended to consume an additional 300-600 mg/h of sodium during prolonged exercise. This recommendation contrasts with guidelines for non-athletes. While the link between sodium and blood pressure (BP) is well-established, studies suggest sodium density, the ratio of sodium to energy consumed, may better predict BP than absolute sodium intake. To our knowledge, no studies have examined these relations in athletes. Hypothesis: We hypothesized that sodium density would be a better indicator of BP when compared to absolute sodium intake and that young athletes would have a higher total sodium intake without a significantly higher BP. Methods: Cross-sectional data were collected from healthy men and women that were stratified into four groups: young collegiate athletes ([YA], n=88, aged 21 ± 2 y), young non-athletes ([YNA], n=36, aged 21 ± 2 y), midlife former collegiate athletes ([MFA], n=82, aged 51 ± 7 y), and midlife non-former athletes ([MNA] n=25, aged 52 ± 7 y). Energy and nutrient intakes were assessed from 3-day dietary records. Anthropometric and BP measurements were collected. Group differences were assessed using a one-way ANOVA with Tukey post-hoc tests. Associations between absolute sodium and sodium density and BP were assessed using Pearson correlations. Results: YA (4102 ± 1490 mg) had a significantly higher sodium intake when compared to YNA (3305 ± 1072 mg), MFA (3159 ± 1154 mg), and MNA (2955 ± 956 mg) (p<0.05 for all). Systolic BP (SBP) was higher in MFA (130 ± 17 mmHg; p<0.05) compared to YA (120 ± 13 mmHg) and YNA (116 ± 13 mmHg). Absolute sodium intake and SBP were positively correlated in YA (r=0.26, p=0.02), YNA (r=0.43, p=0.01) and MFA (r=0.26, p=0.02) but not MNA (r=0.04, p=0.84); however, when corrected for energy intake, these correlations were no longer statistically significant for all groups. Conclusion: These data suggest a weak association between absolute sodium intake and BP in YA. However, when corrected for energy intake this association was no longer present. This may not be specific to YA as this association was also seen in YNA and MFA. Our results highlight the importance of examining both absolute sodium intake and sodium density as it relates to BP in populations with increased energy needs. NIH (DP5 OD031833, R01 HL145055, 2UL1TR001436). 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.
Potassium Supplementation Offsets the Effects of a High Sodium Diet on Endothelial Function but Not Blood Pressure Reactivity in Healthy, Normotensive Adults
Authors: Lobene Andrea J. , Jacintho Moritz Cesar , Kaseman Kathryn E. , Irwin Jessica M. , Zimmerman Matthew C. , Farquhar William B. , Lennon Shannon L. 
Published: May 2024

High sodium diets are linked to endothelial dysfunction and increased blood pressure reactivity (BPR) to physiological stimuli, which are both notable cardiovascular disease (CVD) risk factors. High potassium diets are shown to lower blood pressure (BP) and improve endothelial function; however, previous interventions often increased potassium intake using food, making it diffcult to attribute these effects to potassium alone. The interactive effects of sodium and potassium on pre-clinical CVD risk factors remains unclear. The objective of this study was to determine if potassium can independently counteract the effects of a high sodium diet on endothelial function and BPR in healthy, normotensive adults. We hypothesized that endothelial function and BPR would be impaired with a high sodium diet compared to a low sodium diet but would improve with the addition of potassium supplements. Nineteen participants (13W/6M, age 26±4 y, BP 108±11/71±9 mmHg, BMI 25.1±2.7 kg/m2) completed three 10-day controlled diets in random order: a moderate potassium/low sodium (MK/LS; 55 mmol K/50 mmol Na) diet, a moderate potassium/high sodium (MK/HS; 55 mmol K/300 mmol Na) diet, and a high potassium/high sodium (HK/HS; 120 mmol K/300 mmol Na) diet. Potassium intake was increased using potassium chloride supplements. Dietary compliance was confirmed by urinalysis. On day 10, endothelial function was assessed by brachial artery flow-mediated dilation (FMD), and BPR was assessed by measuring ΔMAP in response to an isometric handgrip exercise (IHG) with post-exercise ischemia (PEI) and the cold pressor test (CPT). Differences across diets were assessed by repeated-measures ANOVA. Twenty-four-hour ambulatory mean arterial pressure (MAP), which was measured on day 9, was not different across diets (MK/LS: 81±5 mmHg; MK/HS: 79±4 mmHg; HK/HS: 80±6 mmHg; p=0.15), indicating our participants were salt-resistant. FMD was significantly lower on the MK/HS diet compared to the MK/LS diet (MK/HS: 5.8±2.8% vs. MK/LS: 8.2±3.7%; p=0.004) and was rescued with the addition of potassium supplements (HK/HS: 8.9±3.2; p=0.009 compared to MK/HS). FMD on MK/LS and HK/HS diets were similar (p>0.05). There were no differences across diets in ΔMAP in response to the IHG (p=0.73), the PEI (p=0.67), or the CPT (p=0.94). Our findings suggest that, while sodium and potassium may not affect BPR, potassium supplementation effectively counteracts sodium-induced endothelial dysfunction in healthy, normotensive, salt-resistant adults. AHA/VIVA 23POST1009835; NHLBI R01 HL145055. 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.
Coronary microvascular dysfunction in postmenopausal minipigs with multiple risk factors
Authors: Sorop Oana , Zandbergen Lotte , van Drie Ruben , Merkus Daphne , Duncker Dirk J. 
Published: May 2024

Coronary microvascular angina occurs in both men and women, however, the majority of patients are postmenopausal women with multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia. No treatment is available for coronary microvascular dysfunction, requiring more in depth knowledge on the mechanisms underlying this syndrome in this expanding group of patients. Here we studied microvascular function in vivo and and in vitro in isolated small coronary arteries, in postmenopausal miniswine with multiple cardiovascular risk factors. DM (streptozotocin), hypercholesterolemia (HC, high fat, high sugar diet), CKD (renal artery embolization) and menopause (OVX) were induced in 5 adult female minipigs (1.5-2 years old, ±40kg, DM+HC+CKD+OVX) for 6 months, while 11 healthy female minipigs matched for age and weight, on normal pig chow served as controls (Control). At sacrifice, coronary flow reserve (CFR) in response to intracoronary infusion of adenosine was measured under anesthesia, and endothelium-dependent response to bradykinin in the presence and absence of eNOS blockade with LNAME, were studied in vitro in isolated small coronary arteries. 6 months of sustained hyperglycemia (17.5±1.0 in in DM+HC+CKD+OVX vs 8.2±0.9 mmol/l in Control), hypercholesterolemia (15.4±2.0 vs 1.7±0.1 mmol/l) and renal dysfunction (plasma total protein: 84±3 vs 72±1 g/l) were accompanied by systemic inflammation (TNFalpha: 62±7 vs 47±1 pg/ml, all p<0.05 by t-test). Coronary flow reserve was significantly reduced in animals with multiple risk factors (3.4±0.4 in DM+HC+CKD+OVX) as compared to the healthy animals (4.9±0.3 in Control, p<0.05). In vitro, coronary small arteries from DM+HC+CKD+OVX animals showed impaired endothelium-dependent vasodilation to bradykinin, which was mediated by a loss of nitric oxide. Conclusion: Postmenopausal minipigs with multiple risk factors, displayed severe coronary microvascular dysfunction as evidenced by a significantly reduced coronary flow reserve and endothelial dysfunction. The latter was characterized by a marked loss of nitric oxide. Such perturbations may contribute to reduced myocardial perfusion that is often observed in postmenopausal women with multiple cardiovascular risk factors. Funding: Grant 2020B008 RECONNEXT. 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.
The Critical Ambient Temperature Threshold for Safe Fan Use in Young Adults During Extreme Heat Exposure
Authors: Mihalcin Emily , Ravanelli Nicholas 
Published: May 2024

Introduction: The electric fan may be an effective, low-cost heat resilience solution during extreme heat. Fans have been shown to attenuate the rise in cardiovascular and thermal strain relative to still air in young adults, particularly during exposure to more humid conditions. When ambient temperature exceeds skin temperature, a fan improves sweat evaporation from the skin surface, which counterbalances the increased rate of convective heat gain. However, at higher air temperatures, the increased convective heat gain may exceed the rate of evaporative heat loss resulting in net heat gain and increasing physiological strain. The purpose of the present study was to identify the critical ambient temperature limit, where increased physiological strain will be observed, with a fan in comparison to still air. Method: To date, 6 participants (4 females; 24±9 y; 72.8±17.8 kg; 1.8±0.2 m) have completed two 180-minute temperature ramp heat-exposures (37°C to 47°C at ~0.05°C/min, 25%RH) on separate days. Wearing standardized t-shirts and shorts, the participants remained seated while either i) facing an electric fan (5.3±0.9 m/s) or ii) in still air (0.1±0.0 m/s). Rectal and skin temperature, heart rate, blood pressure, whole-body sweat loss, thermal comfort, and thermal sensation were measured every 10 minutes. Results: Rectal temperature was similar between fan and still air up to 43°C (P>0.92), however was greater with a fan from 44°C onwards (p<0.05). Skin temperature was higher with a fan compared to still air throughout the exposure (p<0.001). Heart rate was similar between fan and still air until 44°C (P>0.61), after which heart rate was higher with a fan (p<0.05). Mean arterial pressure was not different between fan and still air at any air temperature (P=0.53). The rate pressure product was higher with a fan compared to still air when the ambient temperature exceeded 44°C (p<0.05). Whole-body sweat losses were greater with a fan (1215±250 g) compared to still air (675±103 g, P=0.006). No differences between fan and still air were observed for thermal comfort (P=0.22) or thermal sensation (P=0.73) throughout the temperature ramp protocol. Conclusion: When ambient temperature exceeds 43°C, electric fan use results in greater physiological strain at rest in young healthy adults relative to still air. This research was supported by Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). 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.
Small mesenteric artery passive mechanical properties in adult APOE3 & APOE4 Mice
Authors: McMurray Shelby , Walton Isaiah , Gusek Brikena , Stimpson Anna , Jones Carleton , Eckman Delrae 
Published: May 2024

Previous studies from our lab have demonstrated changes in vascular structure and function in posterior cerebral arteries and left common carotid artery (CA) in adult male and female mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)MaeN8) and APOE4 (B6.129P2-Apoetm3(APOE*4)MaeN8) (Taconic Labs). Therefore, we hypothesized that similar changes may be observed in the systemic circulation. We isolated 4thor 5th-order mesenteric arteries from adult 6-month-old male and female mice expressing hAPOE3 (n=5) or hAPOE4 (n=4). Mesenteric artery segments (5-8 mm in length) were isolated and cannulated on an arteriograph to assess vascular mechanical properties; lumen diameter, wall thickness, wall:lumen ratio, distensibility, stress versus strain (SvS), compliance, incremental modulus of elasticity (Einc), and calculated pulse wave velocity under passive conditions (Ca2+-free Krebs plus diltiazem) at intraluminal pressures ranging from 10mmHg to 140mmHg. In addition, phenylephrine-induced contraction and potassium-induced contraction were assessed using Ca2+-containing Krebs. Data was analyzed using two-way ANOVA, Student’s t-test, and analysis of nonlinear fit. Values were considered statistically different at p<0.05. In our preliminary data, lumen diameter, distensibility, compliance, strain, and calculated pulse wave velocity were similar in APOE3 and APOE4 mice. Wall thickness and wall:lumen ratio were significantly greater in APOE4 compared to APOE3 mice. Wall stress and Einc were significantly less in APOE4 compared to APOE3 mice. Interestingly, the APOE4 mice exhibited a significantly lesser stress per given amount of strain compared to the APOE3 mice. Phenylephrine- and potassium-induced contractions were similar in APOE3 and APOE4 mice. This data suggests there are changes in passive mechanical properties in small mesenteric arteries from APOE4 mice, which resemble a hypertensive phenotype. ABRC/ADHS18-205211 (DME, CBJ), Arizona Alzheimer’s Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (SM, IW, DME), Biomedical Sciences Start-up Funds (DME). 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.
The Proximal Tubule Response to Low Potassium Is Mediated by mTOR/AKT Activation via Kir4.2
Authors: Zhang Yahua , Denton Jerod , Zhang Ming-zhi , Harris Raymond , Terker Andrew 
Published: May 2024

Background: The renal epithelium is highly sensitive to changes in blood potassium (K+) levels. We have a detailed understanding of distal K+-sensitive signaling pathways, yet proximal mechanisms are less well-defined. Results: Mice lacking the basolateral proximal tubule inwardly rectifying K+ channel, Kir4.2, (Kir4.2−/−) demonstrated normal blood and urine electrolytes at baseline. Upon removal of K+ from their diet, Kir4.2−/− animals decompensated as evidenced by increased urinary K+ excretion and development of a proximal renal tubular acidosis compared to control animals (Kir4.2+/+). Potassium wasting in Kir4.2−/− mice was not proximal in origin, but was dependent upon increased ENaC activity along the connecting segment. This was demonstrated by the correction of K+ wasting in knockouts treated with the ENaC inhibitor, amiloride. Using lithium clearance studies, we further demonstrated increased distal sodium delivery in Kir4.2−/− animals due to reduced proximal tubule sodium reabsorption. Optical clearing and three-dimensional confocal imaging reveal Kir4.2−/− mice failed to undergo proximal tubule hypertrophy when fed a low K+ diet, while the distal convoluted tubule response was exaggerated in knockouts compared to control animals. A phosphoproteomics mass spectrometry analysis identified increased mTOR/AKT signaling as mediating the proximal dietary response to K+ depletion in control animals, and changes to mTOR/AKT signaling was blunted in Kir4.2 knockouts. Lastly, we demonstrated in isolated renal tubules that AKT phosphorylation in response to low K+ depended upon mTORC2 activation by secondary reductions in intracellular Cl−. Conclusions: In this work we identify the basolateral inwardly rectifying K+ channel, Kir4.2, as a mediator of the proximal tubule response to K+ deficiency. Kir4.2 knockout mice increase their distal nephron transport burden to maintain electrolyte homeostasis in the face of deficient proximal tubule cell function. Data identify a conserved proximal role for cell Cl− which, as it does along the distal convoluted tubule, responds to extracellular K+ changes to activate intracellular kinase signaling. Along the proximal tubule, mTOR/AKT signaling is essential for the cell response to low K+. Proximal and distal nephron cell Cl− responses work in concert to preserve K+ homeostasis. These studies were supported by NIH grants DP5-OD033412 (AST), DK51265, DK95785, DK62794, DK7569, P30DK114809 (RCH, MZZ), and the Vanderbilt Center for Kidney Disease and Vanderbilt Diabetes Research and Training Center (DK020593) pilot and feasibility grant (JSD). 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.
Timing of acute cold exposure determines thermoregulatory responses - possible interactions between the thermal environment and circadian clocks
Authors: Haugen Fred , KT Phong Chau , Ryan Elin 
Published: May 2024

Introduction: Shift workers are frequently exposed to the harsh combination of night work in a low-temperature environment. In this project, we aimed to determine if acute induction of thermoregulatory markers UCP1 and FGF21 by cold exposure depend on the timing of the exposure, and to investigate if the neural processing of thermal information has a potential role. Methods: Six groups of C57BI/J6 mice (N=8) were habituated for 2 months to a 12 h light/ 12 h dark regiment at thermoneutral temperature 27 °C (TN). After this period, groups were acutely exposed to an ambient temperature of 15 °C (COLD) or a continuation of TN temperature. Temperature exposures of groups were applied at three different time-points of the day lasting for 8 hours before tissues were harvested at ZT4, ZT12 or ZT20 (i.e. 4, 12 or 20 hours after the light is on, respectively). Thermoregulatory markers were measured in plasma, brown adipose tissue (BAT), liver and the peripheral somatosensory neurons in dorsal root ganglion (DRG) using RTPCR and immunodetection. Furthermore, behaviour testing was used to evaluate thermal preference. Results: UCP1 expression increased in BAT from COLD mice, as compared to TN mice. A higher induction of UCP1 was observed at ZT12 than the other time points. Plasma levels of FGF21 were induced acutely in COLD mice at ZT4 and ZT12, compared to the time-matched TN controls, but COLD mice at ZT20 did not display increase of FGF21 plasma levels. Cold exposure affected mRNA expression patterns of core circadian clock components in BAT (Bmal1, Clock, Per1/2/3, Cry1/2, Nr1d1/2), but in liver these transcripts were not affected. Behavior testing showed that COLD mice developed cold tolerance behaviors at ZT4 but less at ZT12. Analyses of gene expression in the somatosensory DRG neurons revealed circadian oscillations of core components and gene regulation due to cold exposure. Summary: In a nutshell, data suggest that the timing of cold exposure might impact physiological and behavioural adaptations to cold environments. This was associated with diurnal variations of gene expression in DRG neurons. Supported with an internal grant at STAMI. 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.