bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Dietary Sodium Intake on Blood Pressure Variability
Authors: Migdal Kamila U. , Watso Joseph C. , Babcock Matthew C. , Robinson Austin T. , Wenner Megan M. , Stocker Sean D. , Farquhar William B.
Published: June 2021

Purpose

Studies in rodents have demonstrated that increased dietary sodium intake elevates blood pressure variability (BPV), independent of changes in resting blood pressure. Clinical studies have shown that increased BPV independently contributes to target organ damage and cardiovascular events. However, the effects of high dietary sodium intake on BPV in young, normotensive adults remains unknown. Therefore, the purpose of this study was to test the hypothesis that increased dietary sodium intake alters BPV in young, healthy adults.

Methods

Fourteen healthy, normotensive adults (7M/7W; age: 25±4 yrs; BMI: 24.7±0.9 kg/m2, Mean‐±SEM) participated in a controlled feeding study that consisted of 10 days of either low‐(LS:1 g sodium/day), medium‐ (MS: 2.3 g sodium/day), or high‐sodium (HS: 7 g sodium/day) diets, in randomized order. The diets were separated by at least a month. Urinary sodium excretion was determined to ensure compliance on diets. Resting beat‐to‐beat BPV was assessed in the laboratory in the supine position for ten minutes. BPV was also derived from 24‐hour ambulatory blood pressure monitoring (ABPM) to assess BPV under free‐living conditions. BPV was calculated as the average real variability index (ARV; the average of the absolute differences between consecutive blood pressure measurements) and as standard deviation (SD).

Results

Twenty‐four‐hour urinary sodium excretion increased in a step‐wise manner from low, to the medium, to the high sodium diets (LS: 34±6 mmol/24 hours, MS: 93±9 mmol/24, HS:275±29 mmol/24 hours, p<0.05). Dietary sodium did not alter laboratory beat‐to‐beat systolic ARV (LS=2.2±0.2 mmHg, MS= 2.0±0.2 mmHg, HS= 2.1±0.2 mmHg, p>0.05) or 24h ABPM systolic ARV (LS=9.4±0.5 mmHg, MS= 9.9±0.4 mmHg, HS=10.3±0.7 mmHg, p>0.05). Dietary sodium also did not alter laboratory beat‐to‐beat systolic SD (LS= 5.4±0.5 mmHg, MS=5.1±0.3 mmHg, HS=5.8±0.6 mmHg, p>0.05) or 24h ABPM systolic SD (LS= 12.1±0.9 mmHg, MS= 13.9±0.7 mmHg, HS= 13.1±0.9 mmHg, p>0.05).

Conclusion

These preliminary data suggest that 10 days of high dietary sodium intake does not alter systolic BPV in young, healthy adults.

Support or Funding Information

NIH Grant 1RO1HL128388

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does T Cell Specific Knockdown of Estrogen Receptor‐α Eliminate Premenopausal Protection from Angiotensin II‐Induced Hypertension?
Authors: Uhlorn Josh , Husband Nathaniel A. , Romero‐Aleshire Melissa J. , Pollow Dennis P. , Uhrlaub Jennifer L. , Nikolich‐Zugich Janko , Brooks Heddwen L.
Published: June 2021

There is extensive evidence that the immune system is required for the development of angiotensin II (Ang II) induced hypertension in males. In contrast, before entering menopause, we have shown that females are protected from T cell‐mediated Ang II hypertension. Following menopause, female protection from T cell‐mediated Ang II hypertension is lost; in the absence of T cells, systolic blood pressure (SBP) responses to Ang II in Rag‐1−/− postmenopausal mice were similar to those seen in premenopausal mice (SBP Δ12 ± 2 mmHg). After adoptive transfer of CD3+ T cells, Ang II significantly increased SBP in postmenopausal females (SBP Δ28 ± 3 mmHg; p<0.05). Thus, we hypothesize that the loss of estrogen in postmenopausal mice eliminates female protection to T cell‐mediated hypertension. Further, we examined if premenopausal protection from T cell‐mediated hypertension was due to T cell‐specific estrogen receptor alpha (ERα) signaling. CD3+ T cells were purified from ERα null mice (ERαKO) and adoptively transferred into cycling, female Rag‐1−/− mice (no T/B cells). Ang II was infused via osmotic mini‐pump for 14 days (490 ng/kg/min). Similar to our previous studies, cycling female Rag‐1−/− mice were resistant to T cell‐mediated Ang II hypertension following T cell transfer from wild type mice (SBP CD3+WT/Ang Δ6 ± 5 mmHg). Additionally, there was no significant difference in SBP when ERαKO T cells were adoptively transferred (SBP CD3+ ERαKO/Ang Δ5 ± 4 mmHg). Flow cytometric analysis of renal CD4+, CD8+, and regulatory Foxp3+ T cells identified that in the absence of ERα, there was an increase in expression of costimulatory receptor CD28 in all three T cell subsets (CD3+ ERαKO/Ang vs. CD3+WT/Ang: CD4+ 138%, CD8+ 144%, Foxp3+ 141%; p<0.05). Our studies suggest that loss of estrogen (menopause) increases female susceptibility to T cell‐mediated hypertension. However, loss of T cell‐specific ERα signaling does not seem to play a key role in premenopausal protection from T cell‐mediated Ang II hypertension.

Support or Funding Information

1. T32HL007249

2. R01HL131834

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Nitric Oxide‐Dependent Mechanisms in Early Sunitinib‐Induced Hypertension
Authors: Witte Jeannine , Mühlbauer Melanie , Braun Diana , Steinbach Antje , Rettig Rainer , Grisk Olaf
Published: June 2021

Sunitinib is an antiangiogenic receptor tyrosine kinase inhibitor used in cancer treatment. A major adverse effect of sunitinib is a rapidly developing hypertension associated with reduced renal nitric oxide (NO) availability and increased renal fractional sodium reabsorption (FRNa). We tested if NO‐dependent regulation of renal hemodynamics and FRNa are compromised and if nitrate supplementation has antihypertensive effects in early sunitinib‐induced hypertension.

Male Wistar rats were treated with sunitinib at 15 mg/(kg*d). Four days after initiation of sunitinib treatment, renal hemodynamics and renal sodium excretion were investigated. Radiotelemetric experiments were performed to study the effects of nitrate supplementation and soluble guanylate cyclase (sGC) activation on arterial pressure. Nitric oxide synthase (NOS) as well as sGC mRNA and protein abundances were studied in renal tissue.

Within four days, sunitinib elicited a 20–25 mmHg arterial pressure rise. NOS inhibition elicited similar reductions in total and renal medullary blood flow in sunitinib‐ and vehicle‐treated rats. NO‐dependent and independent components of endothelium‐dependent renal vasodilation were not compromised in early sunitinib‐induced hypertension. Low dose intrarenal NOS inhibition did not differentially affect FRNa in sunitinib‐ and vehicle‐treated rats. In sunitinib‐treated rats, renal nitrite/nitrate excretion was 60 per cent less than in controls (p < 0.05). However, nitrate supplementation did not reduce arterial pressure and renal sodium balance in sunitinib‐treated rats. While sunitinib treatment had no effects on renal NOS mRNA abundances, it significantly reduced renal cortical sGC α‐ and β‐subunit mRNA abundances as well as renal cortical guanylate cyclase protein expression. Pharmacological sGC activation caused a rapid 15–20 mmHg arterial pressure fall in sunitinib‐treated rats (p < 0.05).

We conclude that the NO‐dependent regulation of renal hemodynamics is largely unaltered in early sunitinib‐induced hypertension despite evidence for reduced NO formation. Reduced renal sGC expression and activity may contribute to the early arterial pressure rise in sunitinib‐induced hypertension and cause its nitrate resistance.

Support or Funding Information

Supported by the German Research Foundation, Grant‐No. KO 4936/2‐1.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
C1qbp, a Novel Cyclophilin‐D Interacting Protein, Regulates Mitochondrial Permeability Transition and Injury In The Heart
Authors: Baines Christopher P. , Alex Linda , Gutierrez‐Aguilar Manuel , Klutho Paula
Published: June 2021

The mitochondrial permeability transition (MPT) pore regulates necrotic cell death following diverse cardiac insults. However, so far the only confirmed component of the pore is Cyclophilin D (CypD). Our laboratory has previously identified Complement 1q‐binding protein (C1qbp) as a novel CypD‐interacting molecule and a negative regulator of MPT‐dependent cell death. C1qbp is an acidic homotrimer with proposed roles in inflammation, cancer progression, biogenesis of respiratory chain components, and overall mitochondrial ultrastructure. However, its effects in the cardiac system remain untested. We therefore hypothesized that “activation” of C1qbp would inhibit MPT in cardiac mitochondria and protect cardiac myocytes against necrotic death. We first identified several putative C1qbp ligands using an in silico screen. Treatment of cultured cardiac myocytes with these ligands dose‐dependently protected the cells against oxidative stress‐induced necrosis. To investigate the effects of C1qbp in the myocardium we generated gain‐ and loss‐of‐function mice. Transgenic C1qbp overexpression resulted in decreased mitochondrial respiration and decreased ATP synthase activity, although to our surprise MPT remained unchanged. Interestingly, C1qbp+/− mice also exhibited decreased basal mitochondrial respiration but in this case MPT was sensitized. Neither overexpression nor depletion of C1qbp significantly affected baseline heart function at 3 months of age. When subjected to myocardial infarction, infarct size was unaffected in the C1qbp transgenic mice, consistent with the lack of an effect on MPT. In contrast infarct size was increased in the C1qbp deficient mice, in line with the sensitization of cardiac mitochondria from these mice to MPT Taken together, our results suggest that C1qbp is required for normal regulation of the MPT pore, mitochondrial function, and sensitivity to injury in the heart.

Support or Funding Information

NIH HL094404

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered Immune Cell Programming in the Kidneys of Obese Dahl Salt‐Sensitive Leptin Receptor Mutant Rats Prior to Puberty
Authors: Shields Corbin Anthony , Poudel Bibek , McPherson Kasi , Garrett Michael , Williams Jan Michael
Published: June 2021

Recently, we reported that the Dahl salt‐sensitive leptin receptor mutant (SSLepRmutant) strain develops renal injury independent of hyperglycemia and elevations in arterial pressure prior to puberty. However, after puberty, the SSLepRmutant strain develops severe hypertension and chronic kidney disease. In preliminary studies, total RNA was isolated and whole transcriptome paired‐end RNA‐sequencing was performed using an Illumina NextSeq 500 from glomeruli of lean SS wildtype (SSWT) and obese SSLepRmutant rats at 6 weeks of age. The analysis revealed that there were differentially expressed genes in immune cell pathways. Therefore, in the current study, we examined whether there were differences in the expression of various cytokines during the development of renal injury that contribute to immune cell programming in SSWT rats (n=4) and the SSLepRmutant strain (n=4) prior to puberty at 4 and 8 weeks of age via the Bio‐Plex Pro Rat Cytokine 23‐Plex Immunoassay. Protein excretion was significantly higher in the SSLepRmutant strain versus SSWT rats at baseline (65±12 and 2±1 mg/day, respectively) and remained markedly elevated over the course of the study (393±43 and 75±17 mg/day, respectively). The kidneys from the 8‐week old SSLepRmutant rats displayed thickening of glomerular basement membranes, mesangial expansion, and renal fibrosis when compared to their wildtype littermates. We detected marked reductions in immune cell regulation in both SSWT and SSLepRmutant rats between 4 and 8 weeks of age. However, within the SSLepRmutant strain that develops renal injury, we observed significant decreases in T‐lymphocyte (T‐cell) programming cytokines from 4 to 8 weeks of age: IL‐1α (1546±55 to 1060±54 ng/mg), IL‐5 (15±1 to 11±0.3 pg/mg), IL‐6 (30±1 to 24±1 pg/mg), IL‐13 (23±20 to 11±1 pg/mg), TNFα (18±2 to 11±1 pg/mg), and IL‐17 (1227±70 to 151±76 ng/mg) respectively. In conclusion, these data indicate that reductions in cytokines responsible for T‐cell programming in the kidney may play an important role in the development of renal injury associated prepubertal obesity.

Support or Funding Information

This work was supported by P20GM104357 and R01DK109133‐01.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Isolevuglandin Peptide Modification and Proteasomal Processing Contribute to Autoimmune‐Mediated Hypertension
Authors: Patrick David M. , Xiao Liang , Barbaro Natalia R. , Ao Mingfang , Ormseth Michelle J. , Stein C. Michael , Kirabo Annet , Harrison David G.
Published: June 2021

An estimated one‐third of the world's population suffers from hypertension. Over the last decade, it has become clear that immune activation contributes to hypertension. Reactive oxygen species (ROS) have been shown to be an important activator of this disease. Isolevuglandins (isoLG) are oxidation products of fatty acids that form as a result of ROS. These molecules adduct covalently to lysine residues of proteins. These modified proteins are presented within the major histocompatibility complex type I (MHC‐I) molecule and activate T‐cells, implying a role of the proteasome in peptide processing. We hypothesized that isoLG‐adducted peptides contribute to hypertension in SLE and that presentation of isoLG within antigen presenting cells is dependent on proteasomal processing. We found that isoLG‐adducted peptides are markedly enriched in CD11c positive monocytes of patients with systemic lupus erythematosus (SLE). Moreover, cells that display both the monocyte marker CD11c and the activated dendritic cell marker CD86 were also enriched with isoLG‐adducts in patients with SLE. This implies that isoLGs may be participating in activation of antigen presenting cells in SLE. In addition to these studies, we found that the proteasome contributes to the presentation of isoLG‐adducted peptides on the surface of dendritic cells. We previously showed that treatment of mouse dendritic cells with the oxidant tert‐butyl hydroperoxide confers isoLG‐mediated sensitivity to hypertensive stimulus in recipient mice. Interestingly, co‐treatment of mouse dendritic cells with TBHP and proteasome inhibitor attenuates surface isoLG presentation without modification of intracellular isoLG. Moreover, using a novel method employing fluorescence resonance energy transfer (FRET), we found that isoLG‐adducted peptides and MHC‐I interact at the intermolecular level on mouse dendritic cells, strongly suggesting that these peptides are indeed presented within MHC‐I molecules. Co‐treatment of these cells with TBHP and proteasome inhibitor significantly reduced the intermolecular interaction of isoLG with MHC‐I. These studies provide novel insight into the mechanism of isoLG‐mediated hypertension. Additionally, they suggest a novel role for proteasome inhibitors in the treatment of this condition.

Support or Funding Information

This work was supported by the Clinical Pharmacology T32 PHS Grant Number 2 T32 GM 7569‐42

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Organometallic Complex Prevents Metabolic Risk Factors in Male Adolescent Rats Consuming a High Fat Diet for 10 Weeks
Authors: Crawford Meli'sa S. , Clark William , Sweazea Karen L.
Published: June 2021

The prevalence of metabolic syndrome has risen 35% since 2012 and over two‐thirds of Americans meet the criteria of obesity, dyslipidemia, hyperglycemia, insulin resistance and/or endothelial dysfunction. Treating metabolic syndrome is a challenge due to increasing consumption of energy dense foods and lack of compliance with dietary or exercise interventions. The aim of this study was to examine the effects of a novel organometallic complex (OMC) on these metabolic risk factors (obesity, hyperglycemia, dyslipidemia, endothelial dysfunction) in rats fed a high fat diet (HFD) for 10 weeks. Six‐week old male Sprague‐Dawley rats were divided into two dietary groups: standard chow or a HFD composed of 60% kcal from fat. Rats were further divided and treated with OMC in their drinking water at one of the following doses: vehicle (0 mg/mL), 0.6 mg/mL or 3.0 mg/mL. High fat feeding for 10 weeks increased body mass (n=5–6, p<0.05), adiposity (n=5–6, p<0.05), and fasting serum glucose concentrations (n=5, p<0.05) of vehicle‐treated rats. OMC did not prevent weight gain or adiposity in HFD‐fed animals. OMC‐treated HFD rats (3.0 mg/mL) had significantly lower fasting serum glucose concentrations compared to HFD‐vehicle rats (n=6, p<0.05) and OMC (3.0 mg/mL) significantly increased HDL‐c in chow‐fed rats (n=6, p<0.05). To examine endothelial dysfunction, isolated mesenteric resistance arteries (100–130 μm, inner diameter) were cannulated and pressurized to 60 mmHg in a vessel chamber. Arteries were then pre‐constricted to 50% of resting inner diameter with phenylephrine in the superfusate then exposed to increasing concentrations of acetylcholine (ACh, 0.0001–100μM). Low dose OMC promoted vasodilation at lower concentrations of ACh in chow‐fed rats compared to vessels isolated from matched vehicle‐treated animals (n=6, p<0.05). Consistent with prior studies, HFD rats developed impaired vasodilation (n=5, p<0.05), whereas both doses of OMC effectively increased endothelium‐dependent vasodilation (n=6, p<0.05). These findings suggest that OMC, particularly at the higher dose evaluated, effectively ameliorated risk factors associated with metabolic syndrome by attenuating hyperglycemia and improving endothelium‐dependent vasodilation in rats fed a HFD.

Support or Funding Information

This study was funded by a grant from Isagenix International, LLC.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Role of AMPK in Sepsis‐Associated AKI
Authors: Li Ying , Hall Elanore , Pham Hai , Singh Prabhleen
Published: June 2021

Acute kidney injury (AKI) significantly contributes to the morbidity and the mortality in critically ill patients. AKI is also an independent risk factor for developing and progression of chronic kidney disease. Effective therapeutic strategies for AKI are limited due to incomplete understanding its pathogenesis. In most eukaryotic cells, AMP‐activated protein kinase (AMPK) functions as a principle sensory protein, which monitors the cellular energy status and mediates metabolic adaptation through increasing ATP level and regulating mitochondrial hemostasis. Sepsis is the most common cause of AKI. Using a mouse s‐AKI model induced by cecal ligation and puncture (CLP), we investigated the role of AMPK in the pathogenesis of sepsis‐associated AKI (s‐AKI) and its underlying mechanisms.

The GFR was measured by FITC inulin clearance method. At 24 hours post‐injury, the GFR was significantly reduced in CLP mice (345±19 vs. 155±35 uL/min; p=0.004). Treatments with AICAR (an AMPK activator) 24 hours prior to CLP significantly improved the GFR. Additionally, mitochondrial function was evaluated using Seahorse. A significantly increased maximum respiration rate observed in CLP mice was abolished by Pre‐treatment with AICAR. Moreover, mitochondrial DNA copy number and expression of PGC1α, a master regulator of mitochondrial biogenesis were initially increased at 4h’ post CLP injury; then significantly decreased at 24h’ post‐injury, suggesting mitochondrial volume and mitochondrial biogenesis were increased shortly after the injury but eventually dropped. Pre‐treatment with AICAR prevented these alterations at both 4 and 24 hours post CLP. Finally, an elevation of glycolysis, a less efficient pathway compared to oxidative phosphorylation, was observed in response to CLP. This elevation of glycolysis was prevented in mice pre‐treated with AICAR, suggesting activation of AMPK may prevent CLP‐induced alteration of mitochondrial metabolism. Increased glycolysis was not seen at 4h’ post CLP surgery (Figure 1).

Our findings provide novel evidence supporting the critical role of activation of AMPK signaling pathway in preventing development and/or progression of AKI induced by sepsis. Activation of AKI may prevent renal dysfunction in s‐AKI through regulating mitochondrial function, biogenesis, and metabolism. AMPK and its signaling pathway may serve as novel therapeutic targets in s‐AKI.

Support or Funding Information

NIH R01DK107852

VA Merit Review BX002175

NIH R03 DK101841

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Carotid baroreflex responses to simulated hypotension are blunted during passive whole‐body heat stress in young women
Authors: Allen Dustin , Huang Mu , Lenz Kelly , Petric Ursa Bezan , Keller David , Davis Scott L.
Published: June 2021

Previous studies have proposed that carotid baroreflex (CBR) function is potentially compromised during heat stress, thus possibly disrupting the ability to maintain arterial blood pressure in the heat (e.g., decreased orthostatic tolerance during hyperthermia). Recently, we demonstrated that CBR function is preserved, if not enhanced, during a passive whole‐body heat stress (WBH) in young healthy men. What remains unknown is how CBR function is impacted by hyperthermia in women. Therefore, the purpose of this study was to test the hypothesis that CBR‐mediated responses are preserved during a passive WBH in young women. Changes in mean arterial pressure (MAP) and HR were assessed in 7 healthy women (age: 21±1 yrs, height: 171±5 cm, weight: 66±5 kg, BMI: 23±2 kg/m2) using 5‐s trials of neck pressure (NP, carotid hypotension) and neck suction (NS, carotid hypertension) ranging from +40 to −80 Torr during normothermia (NT) and WBH (increased core temp ~1.0 °C) conditions. To assess the CBR control of MAP and HR, a separate two‐way repeated measures ANOVA was utilized for 1) hypertensive stimuli (i.e., NS: −20, −40, −60 & −80 Torr) and 2) hypotensive‐stimuli (i.e., NP: +20 & +40 Torr). Additionally, the time‐to‐peak responses for HR and MAP, separately, in response +40 Torr & −80 Torr trials were examined between thermal conditions using paired t‐tests. During WBH, the CBR‐mediated increases in MAP and HR in response to NP were blunted (main effect of thermal condition p=0.02 and p=0.02, respectively). While the CBR‐mediated decreases in MAP in response to NS were not different between thermal conditions (main effect of thermal condition p=0.34), decreases in HR were markedly greater during WBH (main effect of thermal condition p<0.001). Additionally, the time‐to‐peak responses for MAP and HR were not altered between thermal conditions for either NP or NS trials (p > 0.05 for all comparisons). Taken together, these data suggest the CBR control of MAP and HR during simulated hypotension is blunted in females during passive WBH, while the control of MAP and HR seems to be preserved, if not enhanced, during simulated hypertension. Contrary to our findings in young men, these results suggest there are sex differences in CBR function during WBH. This diminished ability to increase MAP and HR in response to a hypotensive stimulus during hyperthermia may be a key component in reduced orthostatic tolerance in females during WBH.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Five Nights of Sleep Restriction Attenuates Microvascular Endothelial Function
Authors: Craighead Daniel H. , Nahmod Nicole G. , Buxton Orfeu M. , Chang Anne‐Marie M. , Alexander Lacy M.
Published: June 2021

Adequate sleep is requisite for optimal physiological function, including microvascular endothelial function. Short‐term sleep restriction (5 hours/night) negatively alters glucose metabolism and may also impair microvascular endothelial function via increased sympathetic nervous system activity and inflammatory pathways. The cutaneous microvasculature represents an accessible, well‐described vascular bed to non‐invasively assess the effects of sleep restriction on microvascular function. Our objective was to evaluate cutaneous microvascular endothelial function during baseline sleep replete conditions (10 hours/night time in bed), after 5 nights of sleep restriction (5 hours/night), and again after 2 nights of recovery sleep repletion. This was part of the Sleep Restriction Study (PI: Chang), an 11‐day inpatient study that took place in the Penn State University Clinical Research Center, during which diet and physical activity were controlled. Eight young, healthy men (23.3 ± 3.4 years) participated in the study. Cutaneous microvascular function was measured utilizing a standardized local skin heating protocol to induce endothelial nitric oxide‐synthase‐dependent vasodilation during all three study phases (baseline, sleep restricted, recovery). Red cell flux (laser Doppler flowmetry) was continuously measured on the ventral forearm at thermoneutral temperature (33 °C) and throughout local heating 0.5°C·5 s−1 to 42 °C until a stable (20 min) plateau had been reached. Red cell flux was normalized to cutaneous vascular conductance (CVC: flux·MAP−1) and expressed as a percentage of maximum CVC (43°C: %CVCmax). Compared to the baseline sleep replete state, the response to local heating was attenuated by 10% after 5 nights of sleep restriction (baseline: 89.2 ± 2.0, restricted: 80.4 ± 3.0 %CVCmax; p=0.045) and fully recovered after 2 nights of recovery sleep (88.7 ± 1.8 %CVCmax; p=0.99 compared to baseline). Maximum CVC was not affected by sleep restriction (all p>0.05). These results suggest that 5 nights of sleep restriction impairs microvascular endothelial function, likely through attenuated nitric oxide‐dependent vasodilation, but that 2 nights of recovery sleep restores microvascular endothelial function in young, healthy men.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Aerobic Capacity, Age and Duration of Disease on Arterial Function in Individuals with Multiple Sclerosis
Authors: Hibner Brooks A. , Griffith Garett , Schroeder Elizabeth C. , Rosenberg Alexander J. , Hilgenkamp Thessa I.M. , Bollaert Rachel E. , Motl Robert W. , Baynard Tracy , Fernhall Bo
Published: June 2021

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system associated with vascular dysfunction and increased risk of cardiovascular disease and mortality. Aerobic capacity (VO2peak) and age are strong predictors of arterial function in a healthy cohort; however, we know very little about the role of VO2peak, disease duration, and age on vasculature in those with MS.

Purpose

To evaluate the role of fitness, duration of disease since diagnosis (Dx) and age on arterial function in individuals with MS.

Methods

56 individuals (Male: 15, 46±12 yrs, BMI: 29.0±6.8) with MS were divided into young (≤50 years) or older (>50 years) groups. The age groups were further delineated by length of Dx, defined as short (≤10 years) or long (>10 years). Brachial blood pressure (BP) was obtained after a 10 minute rest. Resistance artery function was assessed using strain gauge plethysmography. Reactive hyperemia was calculated as the absolute change between resting and peak flow. Carotid artery stiffness was assessed by ultrasound (Beta‐Stiffness Index (β), Elastic Modulus (Ep) and Arterial Compliance (AC)). A maximal incremental cycle test was performed to assess VO2peak.

Results

See Table. Older adults with MS had higher systolic and mean BP (p<0.05). Length of Dx and age did not influence resistance vessel function (p>0.05), however, VO2peak was associated with peak forearm blood flow and peak conductance. Young and older adults with MS exhibited differential responses in large artery stiffness with disease progression, even after controlling for fitness level (β, Ep, AC) (interactions, p<0.05). Older adults had higher arterial stiffness (β, Ep, AC) with shorter disease duration compared to young. However, with longer disease duration, there was no difference between younger and older adults (p>0.05). β and Ep in older adults decreased with progression of MS (p<0.05). Disease duration did not affect arterial stiffness in young adults (p>0.05).

Conclusion

It appears greater fitness can improve resistance artery function in the MS population. Fitness does not influence large artery stiffness in MS, but with age and duration of disease β and Ep are counterintuitively reduced. These findings require further investigation to elucidate the effects of age, VO2peak and length of Dx on vascular function in MS.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Passive mobilization‐induced vascular function adaptations in bedridden oldest‐old.
Authors: Pedrinolla Anna , Pogliaghi Silvia , Colosio Alessandro , Muti Ettore , Cè Emiliano , Longo Stefano , Espositio Fabio , Schena Federico , Venturelli Massimo
Published: June 2021

Background

With aging, vascular function (VF) declines. Furthermore, a conspicuous number of oldest‐old individuals are in chronically bedridden, and literature indicates that chronic immobility exacerbates VF decline. Although studies have suggested that passive mobilization of the limbs (PM) may improve local VF, the effect of PM on nitric oxide (NO)‐mediated VF has not been studied yet.

Aim

To determine whether PM is effective to counteract VF worsening in bedridden oldest‐old. We hypothesized that bedridden patients who underwent a month of PM would have gained significant improvement in NO‐mediated VF.

Methods

Twenty bedridden individuals (86±7 yrs) were randomly assigned to PM or control (CT) group, treated with standard therapies only. PM groups underwent a program of 30 min of passive knee (flexo‐extension) mobilization (4‐week, twice a day/5 days a week) in addition to their standard therapies. Ight before, right after and a month after the treatment, NO‐mediated VF was measured by means of single passive limb movement (sPLM) test.

Results

All PM patients completed all sessions. Concerning sPLM test, right after the treatment PM group improved significantly sPLMpeak (+33%), ΔPLM (+55%), as well as Area Under the Curve (AUC, +200%). However, a month after the treatment, all the assessed parameters have returned close to basal levels. CT group did not exhibit any change in VF.

Conclusion

Results suggest that the reduction in VF exhibited in chronically bedridden oldest‐old individuals can be reversed by a PM program. Whether performed continously, PM seems to be an effective strategy to counteract the deleterious effects of bedridden on VF.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Administration of Atrial Natriuretic Peptide Does Not Modulate Sweating or Cutaneous Vasodilation in Young Men Exercising in the Heat
Authors: McGarr Gregory W. , Fujii Naoto , Kenny Glen P.
Published: June 2021

Atrial natriuretic peptide (ANP) is a hormone secreted by cardiac muscle cells in response to increases in right atrial pressure, which can occur due to changes in blood pressure and blood volume. This hormone is also secreted during acute exercise in both temperate and hot environments and may be released into the blood due to the effects of increased venous return on the heart caused by active muscle contraction under these conditions. However, ANP release is diminished during prolonged exercise, which may ultimately impair heat loss if its release is linked to alterations in cutaneous blood flow and sweating. The current evidence is mixed with respect to a direct role of ANP in modulating cutaneous vasodilation and sweating responses, with some studies demonstrating an effect of exogenous ANP infusion in augmenting these heat loss responses, while others have failed to show any influence of the hormone. Thus, the purpose of this study was to evaluate the effects of intradermal administration of varying doses of ANP on cutaneous vasodilation and sweating responses in healthy habitually active young men exercising in a hot environment. Ten healthy young males (27 ± 6 years) exercised for 50 min at ~55% VO2peak in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC, measured via laser Doppler flowmetry) and sweating (measured via ventilated capsules) were assessed at four dorsal forearm skin sites receiving either lactated Ringer's solution (Control) or one of three ANP doses (0.1 μM, 1.0 μM, 10 μM) via microdialysis. At the end of exercise, CVC was not different between Control (73 ± 14% CVCmax) and 0.1 μM (66 ± 20% CVCmax), 1.0 μM (69 ± 21% CVCmax), or 10 μM (71 ± 18% CVCmax) ANP sites (all P > 0.05). Similarly, sweat rates were not different between Control (1.37 ± 0.43 mg/min/cm2) and 0.1 μM (1.43 ± 0.55 mg/min/cm2), 1.0 μM (1.44 ± 0.41 mg/min/cm2), or 10 μM (1.36 ± 0.37 mg/min/cm2) ANP sites (all P > 0.05). In summary, these results demonstrate that in healthy habitually active young men, intradermal administration of ANP does not augment cutaneous vasodilation or sweating during exercise in the heat. Such findings may indicate that ANP does not have a direct effect on these heat loss responses. Alternatively, it may be the case that endogenous levels of ANP produced under these conditions are sufficient to elicit a maximal effect of the hormone on cutaneous blood flow and sweating in healthy young men, thus masking any direct effects of exogenous administration.

Support or Funding Information

Funding support: Canadian Institutes of Health Research (held by Dr. Kenny).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Predicting Cardiovascular Hemodynamics in Cold and Warm Environments at Rest with Skin and Core Temperature
Authors: Beckett‐Brown Nicholas T. , Dorman Sandra C. , Merritt Thomas , Gagnon Dominique D.
Published: June 2021

Many occupations require workers to be exposed to extreme heat or cold. During prolonged exposure to extreme environments, the cardiovascular system plays a critical role in thermal homeostasis, by adjusting blood flow in peripheral and central vascular beds. Importantly, exposure to either environment, and the concordant blood‐volume redistribution, increases morbidity and mortality from the additional [and often significant] stress on the cardiovascular system. To gain insight on how to predict cardiovascular stress during exposure to extreme environments at rest, this study attempted to build a regression model to examine the influence of progressive, whole‐body skin and core cooling and heating on cardiovascular hemodynamics. Seventeen participants (12 males, 22.9 ± 3.58 years, 174.2 cm ± 7.85 cm, 12.8 ± 6.20 kg fat mass, and 59.3 ± 9.49 kg fat free mass) wearing shorts and a t‐shirt participated in two laboratory sessions: i) progressive heating (22°C to 40°C); and ii) progressive cooling (22°C to 5°C); each aimed to independently influence skin and core temperatures. Cardiovascular hemodynamics data was collected via thoracic electrical bioimpedance, while metabolic and cardiorespiratory variables were assessed via indirect calorimetry. Mean weighted skin (Tsk) and core (Tc) temperature were measured via portable data loggers and a thermocouple, respectively. Mean weighted skin temperatures ranged from 22.7°C to 37.4°C and Tc ranged from 35.5°C to 37.9°C. A stepwise multiple linear regression analysis was conducted using Tsk, Tc, fat free mass, fat mass, sex and age as predictors for cardiovascular hemodynamics changes under thermal stress. The present model explained 24.4% of changes in stroke volume, 27.9% of heart rate, 15.9% of cardiac output and 49.5% of oxygen consumption. Although changes in Tsk and Tc temperature induced by whole‐body cooling and heating at rest accounted for changes in cardiovascular hemodynamics in the model, a significant portion of the variation remained unexplained. Further research is needed to develop a more accurate model to represent changes in cardiovascular hemodynamics under thermal stress.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect Of Chronic Xenon Supplementation On Hematological Parameters, Cardiorespiratory Fitness, and Athletic Performance
Authors: Dias Katrin A. , Lawley Justin S. , Hearon Christopher M. , Hieda Michinari , Sarma Satyam , Hendrix Max , Levine Benjamin D.
Published: June 2021

Objective

Xenon is an inhalational anesthetic with the potential to improve athletic performance and cardiorespiratory fitness via proposed increases in total blood volume. This study aimed to determine the effect of a four‐week xenon supplementation protocol on total blood volume, maximal oxygen uptake (V̇2max) and 3‐kilometre time trial performance in trained individuals.

Methods

Fourteen subjects (32 ± 12 years; 71% male) were assessed for total blood volume through the carbon monoxide rebreathing method, cardiorespiratory fitness via V̇O2max on a treadmill test, and athletic performance using a 3 km time trial. Following baseline assessments, subjects were matched for sex, age and V̇O2max, and were randomised to 12 sessions of gas inhalation over four weeks (2 minutes of inhalation on 3 days per week); 1) xenon, n = 7 (70% xenon, 21% oxygen, 9% nitrogen) or 2) sham gas, n=7 (7% carbon dioxide, 21% oxygen, 62% nitrogen) dosing. Subjects were blinded to group allocation and all outcomes were re‐assessed following the four‐week dosing period. Within‐group mean differences and 95% confidence intervals for outcomes of interest are presented in Table 1. Differences between the xenon and sham gas group over time were tested using two‐way repeated measures ANOVA and are represented by P values.

Results

Xenon and sham groups were equal at baseline for all outcomes of interest (Table 1). Twelve subjects completed the four‐week dosing intervention and are included in the analyses; one subject withdrew after a single xenon dose due to nausea and one subject was withdrawn after one week of xenon inhalation due to adverse symptoms during and after dosing which resembled sleep paralysis. Blinding was equally effective between groups; subjects in the xenon group were 65% certain of group allocation, while subjects in the sham group were 63% certain of group allocation. There were no significant differences between xenon or sham gas groups for changes in total blood volume, V̇O2max, or 3 km time trial performance (Table 1).

Conclusions

Four weeks of xenon inhalation did not result in significant changes in total blood volume, cardiorespiratory fitness or athletic performance in comparison to a sham gas. Given the presence of adverse symptoms in approximately 30% (2 out of 7) subjects and a clear absence of physiological and performance benefits, our findings do not support the use of xenon as a performance enhancing substance.

Support or Funding Information

This study was supported in part by funding from the Partnership for Clean Competition Research Collaborative.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Western Diet (WD) and Ketogenic Diet (KD) Implication on Voluntary Wheel Running
Authors: Kelty Taylor Jacob , Ruegsegger Greg N. , Grigsbee Kolter B. , Booth Frank W.
Published: June 2021

Physical inactivity is closely associated with a multitude of chronic diseases, which can lead to a poorer quality of life and premature death. The mesolimbic dopamine system has been shown to modulate motivation and reward pathways that drive physical activity. High fat diets (HFD) are known to alter pathways in the brain that drive physical inactivity. However, underlying mechanisms still need more exploration.

Objective

The purpose of my study was to exam HFD's lowering of physical activity.

Methods

In this study male and female Wister rats at 7 weeks of age 1) were placed into running wheels and 2) fed a ketogenic diet (KD), western diet (WD), or standard chow diet (SD) chronically for 7 weeks. Previous studies from the literature shows rats on a HFD tend to overeat leading to weight gain that may lead to decreased voluntary running. In order to measure physical activity independently of caloric intake, rats on the KD and WD were only allowed access to same amount of food calories consumed by the SD group.

Results

Despite giving equal caloric amounts, male rats on the KD had attenuated weight gain (p<0.001) compared to rats fed SD after the first week on the diet. Furthermore, female rats on the WD had increased weight gain in comparison to SD group (p<0.01) by week 7. Both male and female rats had a larger percentage body fat on either HFD compared to SD (p<0.01). Female rats on a WD had a significantly higher body fat percentage than female rats fed the KD (p<0.01). All these data suggest HFD's can change energy expenditure and this effect is gender specific. The results also showed gender specificity when looking at voluntary physical activity. Male rats fed either a KD or WD had overall increases in voluntary wheel running (p<0.05) compared to the SD group. Interestingly, female rats on either HFD showed no increase in running; with rats on a WD running significantly less than the SD group in week 7 (p< 0.01). Transcripts in the mesolimbic dopamine system are currently being analyzed.

Conclusion

HFD's alter voluntary running in a gender specific manner in which the male rats in the present study showed an increase in voluntary wheel running, while the females showed no increase in voluntary wheel running with a decrease in running towards the end of the study.

Significance

The present study reveals HFD influences physical inactivity independently of caloric intake in a gender‐specific manner. This study provides novel insights on how to combat physical inactivity to increase quality and quantity of lifespan.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise and Tart Cherry Increase Antioxidant Capacity after High‐Fat Meal Consumption
Authors: Polley Kristine R. , Pegg Ronald B. , Cooper Jamie A.
Published: June 2021

Background

Exercise and high phytonutrient foods have the potential to combat negative effects associated with a high‐fat (HF) meal by lowering postprandial oxidative stress and increasing antioxidant capacity.

Methods

Thirteen normal weight men (18–30 y), participated in a randomized cross‐over design of four trials: 1) HF meal plus Montmorency tart cherry (C), 2) HF meal plus placebo (P), 3) prior exercise to a HF meal plus Montmorency tart cherry (EC), and 4) prior exercise to a HF meal plus placebo (EP). For exercise trials, a 30 min bout of submaximal treadmill running was performed the afternoon prior to the HF test meal. The HF meal contained 920 kcals and 60 g of fat, with the total percent of calories coming from fat being 59%. Antioxidant capacity of plasma was measured at fasting, and 1, 2, and 3 hours postprandially.

Results

Postprandial oxygen radical absorbance capacity (ORAC) was significantly greater in the CE vs. PE trial (incremental area under the curve (iAUC): 4.10±1.59 vs. −0.58±1.70 mmol Trolox/L/3h, for CE vs. PE, respectively; p < 0.05). There were no other ORAC or postprandial ferric reducing ability of plasma (FRAP) differences between trials.

Conclusion

The CE trial resulted in greater postprandial antioxidant capacity compared to the PE trial as measured by ORAC. The lack of differences found using the FRAP assay indicates that Montmorency tart cherry consumption reduces oxidative stress primarily through a hydrogen atom transfer mechanism, as indicated through ORAC, rather than a single electron transfer as measured with FRAP.

Support or Funding Information

Research was supported by a seed grant from the AU/UGA Medical Partnership and UGA Clinical and Translational Research Unit.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mu opioid receptors inhibit the exercise pressor reflex by closing N‐type calcium channels but not by opening GIRK in rats.
Authors: Estrada Juan A. , Kaufman Marc A.
Published: June 2021

Mu opioid G‐protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N‐type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect. In decerebrate rats, we determined the effect of intrathecal injection of either tertiapin LQ, which blocks the GIRK channel or ω‐conotoxin‐GVIA, which blocks the N‐type calcium channel on the exercise pressor reflex which was evoked by contracting the triceps surae muscles. Initially, we established that intrathecal injection of DAMGO, highly selective MOR agonist, inhibited the exercise pressor reflex relative to no intrathecal injection or intrathecal saline injection (P<0.001, n=5). We then found that intrathecal injection of two doses of tertiapin‐LQ (1 and 10 μg), a GIRK blocker, had no effect on the exercise pressor reflex (n=6 and n=7, respectively; P> 0.05). Importantly, neither dose of tertiapin‐LQ prevented the DAMGO‐induced inhibition of the exercise pressor reflex. Last, we found that intrathecal injection of ω‐conotoxin‐GVIA, an N‐type calcium blocker, markedly attenuated the exercise pressor reflex (P<0.001, n=7). The cardioaccelerator response to contraction did not appear to be effected in any of the experiments. We conclude that N‐type voltage‐gated calcium channel inhibition appears to be the mechanism by which MOR activation inhibits the exercise pressor reflex in decerebrate rats.

Support or Funding Information

This work was supported by NIH grants R01 AR 059397 and P01 HL 134609.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.