bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Acute Antioxidant Cocktail Combined with a High Sodium Meal on Arterial Stiffness and Wave Reflection
Authors: Smiljanec Katarina , Mbakwe Alexis U. , Lennon Shannon L. 
Published: June 2021

Vascular dysfunction is a non‐traditional risk factor for cardiovascular disease (CVD). Further, increased arterial stiffness and wave reflection are considered independent predictors of CVD. High dietary sodium intake has been shown to impair vascular function through an increase in oxidative stress. Therefore, the objective of this study was to investigate the acute effects of an antioxidant cocktail combined with a high sodium meal on measures of arterial stiffness and wave reflection. Twenty‐six young healthy adults (11M, 15F; 22.8 ± 0.5 years; BMI 23.1 ± 0.4 kg/m2; systolic blood pressure 116 ± 2 mmHg, diastolic blood pressure 70 ± 1 mmHg) completed two trials separated by at least 48 hours. All subjects were fasted for 4 hours and women were tested during the early follicular phase of the menstrual cycle. Carotid‐femoral pulse wave velocity (PWV) and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were performed. Aortic augmentation index (AIx), an index of wave reflection, was calculated from the aortic pressure waveform. Participants ingested either two doses of an antioxidant cocktail (AO; each capsule contained 500 mg vitamin C, 300 IU vitamin E, and 300 mg alpha‐lipoic acid) or a placebo (PLA; cellulose). Dose one was consumed 30 min prior and dose two was consumed with the meal. The high sodium meal (1500 mg Na+) consisted of tomato soup with added table salt. Mean arterial pressure (MAP), AIx, and PWV were measured at baseline (BSL) and 30, 60, 90, and 120 minutes after meal consumption. Baseline measurements of AIx did not differ between the two visits (P > 0.05) but decreased over time in both trials (AO: BSL: 8.0 ± 1.4%, 60 min: 2.0 ± 1.3%; PLA: BSL: 6.2 ± 1.4%, 60min: −0.8 ± 1.9%; P‐time effect < 0.001). PWV was not different at baseline (AO: 5.3 ± 0.1 m/s, PLA: 5.2 ± 0.1 m/s; P > 0.05) nor did it change during the two trials (P > 0.05). Similarly, MAP was not different at baseline (P > 0.05) and it remained unchanged during the two trials (P > 0.05). In conclusion, acute consumption of a high sodium meal did not impair arterial stiffness or wave reflection in young, healthy adults.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 Salt Taste Threshold on Cardiovascular Response to Isotonic Exercise in Young Adults
Authors: Elias Simiat O. , Quadri Taofeek O. , Bamiro Saka A. , Umoren Grace A. 
Published: June 2021

Increased salt intake among persons with high salt taste threshold may lead to exercise‐induced hypertension and eventually arterial hypertension. Salt sensitivity has been demonstrated among our populace. This study was designed to investigate the effect of salt taste threshold (STT) on cardiovascular response to exercise. The study protocol was carried out in accordance with the Declaration of Helsinki. Forty‐seven normotensive individuals participated in the study after giving informed consent. Baseline blood pressure, BP (mmHg) and heart rate, HR (beats/min) were determined in all subjects. Salt taste threshold (STT) was determined by making subjects taste increasing concentrations (15mmol/L–105 mmol/L) of NaCl prior to exercise and subjects were divided into Low salt tasters (LST, <60 mmol/L) and high salt tasters (HST, >60 mmol/L). Each participant completed 6 minutes of isotonic (Havard Step Test) exercise. Data were analyzed using Student t test with GraphPad Prism version 5. Significance was accepted at p<0.05. There were 39(83%) LST and 8(17%) were HST. Isotonic exercise led to significant increases in systolic (116±1 to 139±2 mmHg; p<0.0001) and diastolic (73±2 to 88±3 mmHg; p = 0.0007) BP; as well as HR (71.61±3.73 to 99.61±1.85; p<0.0001). However, the magnitude of the pressor response (%Δ) of high STTs to isotonic exercise was not different (p>0.05) from that of LSTs. Similarly, the %Δ in HR response of HST to isotonic exercise was not different (p=0.898) from that of LSTs. Plasma sodium (7.42 ±0.42 mmol/L) was higher in HSTs (p<0.0001) than that in Low salt tasters (6.48± 0.23 mmol/L). We conclude that salt sensitivity did not seem to affect response to isotonic exercise.Support or Funding InformationSelf‐fundedThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High resolution ultrasound imaging reveals cardiac and vascular dysfunction in the 3xTG mouse model of Alzheimer's disease.
Authors: Hoxha Brikena , Talley Nicholas , Anderson Miranda , Alkhouli Mustafa , Squire Michaela , Esfandiarei Mitra , Broderick Tom L. 
Published: June 2021

Alzheimer's disease (AD) is a devastating neurodegenerative disease. Recent clinical studies have demonstrated that patients with AD exhibit compromised cardiac function. In this study, we investigated whether the 3x‐Tg mouse model of AD also presents with cardiovascular dysfunction. This model develops age‐related neuropathology including plaques and tangles, synaptic dysfunction, and amyloid‐beta deposits by six months. In vivo cardiovascular function, determined by echocardiography, was performed in seven‐month‐old male 3xTg mice (n=7) and age‐matched controls (n=8) under isoflurane‐induced anesthesia. While body weight was lower in AD mice compared to control mice, no differences in heart weight were observed between groups. There were no differences in aortic structure, expressed as aortic annulus, sinus of Valsalva, and sinotubular junction between groups. Ventricular dimensions, measured as interventricular septal end diastole and end systole, were also similar between groups. However, ejection fraction was lower in AD mice, whereas early (A) and late (E) atrial ventricular filling velocities, the E/A ratio, and mitral valve deceleration time were increased compared to control mice. In AD mice, pulse wave velocity was increased, which is indicative of increased stiffness and reduced elasticity of the aorta. We observed a significant increase in elastin fiber fragmentation within the media of the aorta, which was associated with overall decreased elastin content and fiber length. Aorta from AD mice also exhibited pronounced medial and adventitial wall thicknesses compared to control mice. Our results provide novel information on structural and functional properties of the heart and aorta in the 3x‐Tg mouse model of AD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Central Nucleus of the Amygdala Mediates Sympathoinhibitory Responses to Activation of Paraventricular Nucleus of the Thalamus
Authors: Puigbonet Maria E. , Li Zhouhui , Ciriello John 
Published: June 2021

The paraventricular nucleus of the thalamus (PVT) is known to relay sensory information from the brainstem, and information from limbic and cortical structures involved in visceral and homeostatic regulation, and affective behaviors. In turn, PVT relays this information to a number of forebrain structures, including the amygdala. However, whether PVT is involved in mediating cardiovascular information to other central sites is not clear. This study was done to investigate whether the cardiovascular responses elicited by PVT involved a pathway that included the central nucleus of the amygdala (ACe). In the first series of experiments, a systematic mapping of PVT was done to identify cardiovascular responsive sites using microinjection of glutamate (Glu; 10 nL, 0.25 M) in chloralose anesthetized Wistar rats. Glu injections into PVT elicited decreases in systemic mean arterial pressure (MAP, −20 ± 3 mmHg) and heart rate (HR; −15 ± 5 bpm). These depressor responses were mediated through sympathoinhibition as intravenous injections of the ganglionic blocker hexamethonium bromide prevented the responses. In the second series, iontophoretic injections of the anterograde tract tracer PHA‐L were made at PVT depressor sites in the Wistar rats. Dense PHA‐L fiber and presumptive terminal labeling was found within and around the region of the lateral ACe, while light to moderate labeling was observed within the medial ACe. Additionally, extensive labeling was observed throughout the extended amygdala, including the bed nucleus of the stria terminalis. In the final series, bilateral microinjection (100 nL) of either the synaptic blocker CoCl2, the non‐specific glutamate antagonist kynurenic acid or the specific NMDA receptor antagonists 2‐amino‐5‐phosphonovalerate or MK801 were made into ACe in the chloralose anesthetized Wistar rats. Injections of these compounds did not significantly alter the resting levels of arterial pressure (AP) or HR, but significantly attenuated (p<0.01) the MAP response (mean of all injected compounds; −7 ± 5 mmHg) to activation of PVT. On the other hand, these injections into ACe did not alter the HR response (mean of all injected compounds; −12 ± 3 bpm) to PVT stimulation. These data suggest that PVT may function as a relay of sensory information that affects AP responses associated with motivated and addictive behaviors, arousal and/or stress through a sympathoinhibitory neural circuit involving ACe.Support or Funding InformationSupported in part by Heart and Stroke Foundation of Ontario.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kidney‐Specific COP9 Signalosome (CSN) Deletion Mimics FHHt Effects on WNK/NCC Signaling
Authors: Cornelius Ryan J. , Yang Chao‐Ling , Ellison David H. 
Published: June 2021

The Familial Hyperkalemic Hypertension (FHHt) cullin 3 (CUL3) mutant is unable to degrade WNK kinases normally, activating the thiazide‐sensitive NaCl cotransporter (NCC). Previous in vitro work showed that the CUL3 mutant has enhanced neddylation and does not bind to the COP9 signalosome (CSN), a deneddylase involved in regulating cullin‐RING ligases. We sought to determine whether this impaired binding was the cause of the increased WNK protein abundance in FHHt by inhibiting the CSN in vivo. The Pax8 mouse system was used to generate mice in which the catalytically active CSN subunit, JAB1, was deleted only along the nephron, after full development (KS‐Jab1−/−). JAB1 protein abundance was 62% lower in KS‐Jab1−/− kidney vs control. Western blot analysis demonstrated that loss of JAB1 caused enhanced neddylation of CUL3. Moreover, total CUL3 abundance was reduced by 37%, indicating decreased CUL3 stability, which is consistent with results reported by other groups for the FHHt CUL3 mutant. As expected, KLHL3 protein abundance was lower and total WNK1 and WNK4 protein abundance were higher. Phosphorylated WNK4 levels and the ratio of pNCC to total NCC were also higher, but, surprisingly, total NCC protein abundance was dramatically reduced. Consistent with the low total NCC, KS‐Jab1−/− mice did not develop an FHHt phenotype. Blood pressure was not significantly different between the two groups. KS‐Jab1−/− mice had lower plasma [K+] (3.20 ± 0.07 vs 3.55 ± 0.06 mM, P < 0.01), lower plasma bicarbonate ([TCO2]: 11.83 ± 0.87 vs 18.00 ± 0.57 mM, P < 0.001), and higher plasma [Cl−] (117.5 ± 1.7 vs 112.7 ± 1.3 mM; P < 0.05) compared to control mice. Urine output was approximately twice as high in KS‐Jab1−/− mice (9.4 ± 1.6 vs 4.7 ± 0.50 ml/day, P < 0.05), and there was Na+ and K+ wasting (Na+ clearance: 0.135 ± 0.013 vs 0.088 ± 0.006 ml/day/g, P < 0.01; K+ clearance: 4.90 ± 0.40 vs 3.68 ± 0.28 ml/day/g, P < 0.05). As we reported with CUL3 deletion, chronic JAB1 deletion also led to kidney tubule damage, as determined by H&E staining. In conclusion, KS‐Jab1−/− mice resemble many aspects of the FHHt CUL3 mutant, including changes in KLHL3 and WNK abundance, and increased phosphorylation of WNK and NCC; however, due to decreased levels of total NCC, the mice do not mimic all aspects of the FHHt phenotype.Support or Funding InformationNIH R01 DK51496, NIH T32 DK067864, VA 1I01BX002228‐01A1, AHA 16POST3064003, NIH F32 DK112531This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myocardial Hypersensitivity to Ischemic Injury is not Blocked by Clonidine or Propranolol in a Predator‐Based Model of PTSD
Authors: Rorabaugh Boyd R. , Stoops Thorne , Rose Robert M. , Kohls Brooke A. , Heikkila Megan E. , Hertenstein Brooke J. , Robinson Kiera L. , Mucher Kasey E. , Huntley Maddy R. , D'Alessio Paul A. , Zoladz Phillip R. 
Published: June 2021

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for cardiovascular disease. We previously reported that a predator‐based psychosocial stress model of PTSD led to myocardial hypersensitivity to ischemic injury. Heightened sympathetic signaling has a well‐established role in the formation of anxiety and fear‐related memories associated with PTSD. In addition, chronic β‐adrenergic signaling is known to increase myocardial sensitivity to ischemia. Thus, we examined whether suppression of sympathetic signaling would protect the ischemic heart in rats subjected to the psychosocial stress model of PTSD. Male Sprague‐Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures (separated by 10 days) and subjected to daily social instability throughout the 31 day paradigm. Control rats were handled daily but were not exposed to the cat or to social instability. In the first set of experiments, rats received daily intraperitoneal injections of either clonidine (0.05 mg/kg) or saline beginning on day 2 and continuing through day 31. Rats were tested for anxiety‐like behavior on the elevated plus maze (EPM) on Day 32. Hearts were isolated on day 33 and subjected to 20 minutes ischemia and 2 hours reperfusion on a Langendorff isolated heart system. Stressed rats exhibited increased anxiety‐like behavior on the EPM, as well as significantly larger myocardial infarcts following ischemia. Clonidine reversed the anxiety‐like behavior on the EPM, but had no effect on infarct size. In a second set of experiments, half of the rats were given propranolol (0.5 g/l) in their drinking water starting on day 2 and continuing throughout the 31 day psychosocial stress paradigm. Propranolol had no effect on either anxiety‐like behavior or infarct size. These findings suggest that the increased myocardial sensitivity to ischemic injury observed in this rat model of PTSD is not caused by increased sympathetic tone or by chronic β‐adrenergic receptor signaling.Support or Funding InformationThis work was supported by R15HL132322 to B.R.R.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Genetic Insufficiency of 12/15LOX in Mice‐Facilitated Angiogenic Response Post‐Myocardial Infarction
Authors: Collier MeMe , Halade Ganesh V. 
Published: June 2021

12/15 lipoxygenase (12/15LOX) is a fat‐metabolizing enzyme that uses different fatty acids to form bioactive lipids in pathology of diseases such as myocardial infarction (MI)‐induced heart failure (HF). 12/15LOX‐null mice show an effective healing pattern with a higher survival rate as compared to wildtype (WT), but the mechanism is unknown. We aimed to test whether 12/15LOX expression in wildtype mice impairs angiogenesis of infarcted myocardium post‐MI in acute and chronic HF. MI was surgically induced in wildtype (WT; C57BL/6) and 12/15LOX‐null mice (2–4 months old) by ligating the left anterior descending artery. Mice LV tissues were stained using biotinylated Griffonia (Bandeiraea) Simplicifolia Lectin at acute (day; d1 and d5) and chronic (d28 and d56) time points suggestive of chronic HF post‐MI. To determine angiogenesis, LV 40X images of the remote and peri‐infarct regions were analyzed using light microscopy and then quantified blood vessel density (BVD). As expected, non‐MI naive controls (d0) had the largest BVD compared to remote and peri‐infarct regions of WT and 12/15LOX‐deficient mice post‐MI. BVD diminished in WT and 12/15LOX‐deficient mice at d1. In the remote region, 12/15LOX‐deficient mice had a higher BVD than WT on d5, d28 and d56. BVD peaked on d5 for 12/15LOX‐deficient mice and on d28 for WT. In the peri‐infarct region, 12/15LOX‐deficient mice showed higher BVD than WT on days 1, 5, 28 and 56. BVD peaked on d5 in 12/15LOX‐deficient and WT mice post‐MI. BVD data indicated that angiogenesis peaks on day 5 (during the acute phase) in 12/15LOX‐deficient mice as compared to WT post‐MI. In summary, the presented results suggest that 12/15LOX delay angiogenesis post‐MI in HF.Support or Funding InformationThis research was supported in part by the American Physiology Society to MC as a STRIDE fellow and a grant from the National Heart, Lung and Blood Institute to GVH (HL132989).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of neuronal discharge in the thoracic spinal cord during cardiac stress in a porcine model
Authors: Dale Erica A. , Kipke Jasmine P. , Sunshine Michael D. , Kubo Yukiko , Castro Peter A. , Ardell Jeffrey L. , Mahajan Aman 
Published: June 2021

Sudden cardiac death is the leading cause of death in the United States and is often caused by ventricular tachyarrhythmias (VT; Mozaffarian et al., 2015). Myocardial ischemia triggers imbalances in sympathetic and parasympathetic modulation, via the autonomic nervous system, and leads to the pathophysiology of cardiac arrhythmias. However, the spinal mechanism of this sympathetic neural control remains poorly understood. We hypothesize that cardiac stressors elicit distinct neural signatures in the dorsal horn (DH; the spinal relay point for cardiac afferents) and the intermediolateral (IML) nucleus of the thoracic spinal cord (the primary nexus for modulation of sympathetic efferent outflow). Adult, anesthetized Yorkshire pigs (n=9; 42 ± 1.6 kg) were implanted with high‐density microarrays (64–256 electrodes; Neuronexus) in the thoracic spinal cord to record extracellular potentials. Antidromic stimulation of the T2 paravertebral chain allowed identification of sympathetic preganglionic neurons located in the IML (53 of total 1,757 neurons recorded). To characterize neuronal discharge, after a baseline recording, pigs repeatedly received: 1) chest scratch (SCR), 2) heart touch (THR), 3) ligation of the left anterior descending coronary artery (LAD), 4) occlusion of the inferior vena cava (IVC), or 5) occlusion of the descending aorta (AOC). Preliminary investigation of percent change in firing rate from baseline suggests complex neural signatures in DH and IML neurons during perturbations. A subset of DH neurons increased firing rate during SCR (8.29% of DH neurons), THR (10.70%), LAD (14.40%), IVC (21.57%), and AOC (6.13%). Firing rate increased in a subset of IML neurons as well (3.84% during SCR, 26.92% during THR, 18.87% during LAD, 20.75% during IVC, and 12.12% during AOC). In contrast, firing rate decreased in 4.89% of DH neurons during SCR, 20.88% during THR, 21.63% during LAD, 16.44% during IVC, and 9.85% during AOC. Additionally, rates decreased in a small population of IML neurons (3.84% during SCR, 7.69% during THR, 28.30% during LAD, 5.66% during IVC, and 18.18% during AOC). Subsequent analysis revealed positive correlations between DH and IML neurons, indicating excitatory neuronal connectivity. Further investigation is warranted to understand the temporally related discharge patterns as well as the inhibitory or excitatory nature of these connections. These preliminary data pave a potential pathway to develop targeted neuraxial interventions in cases of intractable ventricular arrhythmia.Support or Funding InformationHL084261, T32‐HD043730This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Crosstalk between Thyroid Hormone Signaling and β‐adrenergic Signaling in Myocardial Infarction
Authors: Zhang Kuo , Tang Yida , Zhang Youhua , Ojamaa Kaie , Saini Amandeep Singh , Carrillo‐Sepulveda Maria Alicia , Gerdes A. Martin 
Published: June 2021

BackgroundBeta blockers form one of the mainstay therapies for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Although THs interact with the sympathoadrenal system at various levels, crosstalk between TH signaling and β‐adrenergic signaling remains poorly understood. We compared pathophysiologic and TH‐adrenergic signaling changes between therapeutic doses of triiodothyronine (T3) and metoprolol (Met) in rats with MI.MethodsFemale Sprague‐Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/d) or Met (100 mg/kg/d) were given in drinking water immediately after surgery for 8 weeks. At terminal experiments, rats were subjected to morphological, functional, and molecular examination.ResultsT3 and Met significantly enhanced left ventricular (LV) fractional shortening (LVFS 21.4±2.6% and 21.1±3.7%, respectively) compared to untreated MI (17.9±1.2%) and decreased the incidence of inducible atrial tachyarrhythmia by 87.5% and 62.5% without producing untoward effects. Although both treatments showed efficacy, T3 but not Met showed statistically significant improvements compared to MI in arrhythmia duration, left atrial diameter (T3 vs MI 4.3±0.6 vs. 5.7±1.3 mm, p<0.05; Met 4.9±1.1), fibrosis (6.1±0.6%, 6.6±0.6% vs. 8.2±0.7%, T3, Met vs. MI, respectively) and aortic vasorelaxation responsiveness (pD2 6.97±0.22, 6.83±0.21 vs. 6.66±0.22, T3, Met vs MI, respectively). Quantitative PCR showed that T3 and Met attenuated expression of genes associated with inflammation and oxidative stress and restored expression of ion channels and contractile proteins compared to MI rats. Importantly, thyroid and β‐adrenergic signaling genes were favorably regulated by both treatments.ConclusionThese results support comparable efficacy of long‐term treatment with a physiological dose of T3 that is comparable to Met and suggest a potential therapeutic alternative to standard β‐blockade for patients intolerant to treatment with β‐blockers after MI.Support or Funding InformationThis work was supported by the National Heart, Lung, and Blood Institute of the NIH, Bethesda, MD, under Award Number R01HL103671 (AG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We also acknowledged the National Natural Science Foundation of China (No. 81470485), Capital Clinical Featured Application Research Project (NO. z151100004015175) and CAMS Innovation Fund for Medical Sciences (CIFMS 2016‐I2M‐1‐009).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.