bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial baroreflex control of sympathetic nerve activity during acute hypotension is enhanced in young normotensive black men
Authors: Holwerda Seth W , Keller David M , Credeur Daniel P , Fadel Paul J 
Published: June 2021

Although impairments in arterial baroreflex (ABR) control of heart rate have been reported in black compared to white subjects, no studies have examined the potential for racial differences in the ABR control of muscle sympathetic nerve activity (MSNA). Therefore, we tested the hypothesis that ABR control of MSNA is impaired in young black men compared to white men. In 12 non‐hypertensive men (7 black and 5 white, age 18–27 yr) ABR control of MSNA was determined using 100μg i.v. of sodium nitroprusside (NTP) followed 1 min later by 150μg of phenylephrine (PE) during supine rest (3 trials/subject). The slope of the relationship (i.e., gain) between changes in diastolic blood pressure and MSNA was determined. Overall sympathetic baroreflex gain was not different between racial groups (blacks: − 1.9±0.2 vs. whites: −2.4 ± 0.4 AU·beat·mmHg−1, p>;0.05). Similarly, sympathetic baroreflex gain for hypertension (PE phase) was also not different between groups (blacks: −1.9±0.3 vs. whites: −1.7±0.2 AU·beat·mmHg−1, p>;0.05). However, sympathetic baroreflex gain for hypotension (NTP phase) was significantly elevated in blacks (−4.0±0.3) compared to whites (−3.2±0.1 AU·beat·mmHg−1, p<0.05). In contrast to our hypothesis, these preliminary findings suggest that ABR control of MSNA is similar or enhanced in young blacks compared to their white counterparts.Supported by NIH Grant R15HL096103 (DMK) and RO1 HL093167 (PJF)
Behavioral Profile Assessment in Offspring of Swiss Mice Underwent to Neonatal Treatment with D‐fenfluramine
Authors: Melo Roberto Laureano , Silveira Anderson Luis Bezerra , Seara Fernando Azevedo Cruz , da Rocha Fabio Fagundes , Reis Luis Carlos , Cortes Wellington Silva 
Published: June 2021

Serotonin (5‐HT) exerts an important role in the central nervous system embryogenesis of mammals, influencing directly several brain systems ontogeny. Therefore, we investigate the effect of neonatal D‐fenfluramine (D‐fen), a specific 5‐HT‐releasing agent, administration on the behavioral expression of adults male Swiss mice. For this purpose, three groups (n=6 each, and ~35g) of pregnant female Swiss mice were mated. The offsprings obtained were treated subcutaneously (s.c) with saline and D‐fenfluramine (1mg/kg or 3mg/kg) from the 5th at 21th post‐natal day. By completing 70 days of life, the animals underwent a behavioral assessment in open field, rotarod, light‐dark box, elevated plus maze and tail suspension test. Statistical analysis was performed by ANOVA one way and the means were considered significantly different when p<0.05. According to our results, the programmed animals had less time of immobility in tail suspension test (D‐fen 3mg/kg: 64.89±6.07; D‐Fen 1mg/kg: 94.15±9.67 vs. control: 130.6±13.26, p<0.001) and less time spent walking on rotarod (D‐fen 3mg/kg: 17.55±7.32; D‐Fen 1mg/kg: 22.75±7.90 vs. control: 189,7±52,33, p<0.001). In the dark light box test, the animals treated with D‐fen 3mg/kg had less time in the light side than the other groups (D‐fen 3mg/kg: 94,56±8.81 vs. D‐Fen 1mg/kg: 121.7±3.43; control: 133.9±8.01, p<0.01). These findings suggest that programming with D‐fenfluramine during the neonatal period alters neural circuits involved with coordination, anxiety and depression‐like behaviors in adults.Support: FAPERJ & CNPq.
The role of TNF‐α in cardioprotection induced by adaptation to chronic hypoxia in rats.
Authors: Neckar Jan , Chytilova Anna , Borchert Gudrun H , Kolar Frantisek 
Published: June 2021

It has been reported that tumor necrosis factor (TNF‐α) can precondition the heart against acute ischemia/reperfusion injury. This study examined if TNF‐α also plays a role in a long‐lasting cardioprotection induced by chronic hypoxia. Adult male Wistar rats were exposed for 30 days to chronic continuous hypoxia (CCH; inspired O2 fraction 0.1); half of the animals were treated with a TNF‐α inhibitor infliximab (5 mg/kg i.p. once a week). Controls were kept at room air and treated in a corresponding manner. CCH increased the concentration of TNF‐α in particulate fraction of the left ventricle while the concentration of interleukin 10 (IL‐10) and the ratio of IL‐10 to TNF‐α decreased in both cytosolic and particulate fractions. Myocardial infarct size induced by 20‐min coronary artery occlusion and 3‐h reperfusion was reduced in CCH rats by 33% as compared with normoxic controls. This protective effect was attenuated in animals treated with infliximab, which had no effect in normoxic controls. The results suggest that adaptation to CCH results in the myocardial inflammatory response and TNF‐α is involved in the cardioprotective mechanism.Supported by grants GAAV IAAX01110901, GACR 303/12/1162.
Analysis of mitochondrial MMP‐2 and MMP‐9 in the heart
Authors: Hughes Bryan , Fan Frank (Xiaohu) , Simmen Thomas , Schulz Richard 
Published: June 2021

Matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 have been reported to be in cardiac mitochondria. However, these studies relied on non‐specific immunological methods or crude mitochondrial fractions contaminated with endoplasmic reticulum (ER). To determine if MMP‐2 and ‐9 are in the mitochondria we isolated purified mitochondria from adult rat hearts via Percoll density gradient centrifugation. To confirm mitochondrial purity, we showed that the ER marker protein disulfide isomerase, present in crude mitochondria, was absent in the Percoll‐purified mitochondrial fraction. We detected 72 kDa MMP‐2 via gelatin zymography and western blotting in crude mitochondrial fractions; MMP‐9 was only detected by western blotting. Purified mitochondria did not exhibit MMP‐2 or ‐9 gelatinolytic activities, but showed both MMP‐2 and MMP‐9 protein in western blots. In conclusion, MMPs are present in cardiac mitochondria, however, they appear to be in a form that may be resistant to activation. Future research will investigate several putative mitochondrial targets of MMPs identified by previous non‐biased degradomic screens.Funding: Canadian Institutes of Health Research
Both collagen and elastin matrices are remodeled in the failing ovine atria – a role for elastin‐degrading enzymes in atrial structural remodeling
Authors: Horn Margaux A , Graham Helen K , Borland Samantha J , Clarke Jessica D , Dibb Katharine M , Trafford Andrew W 
Published: June 2021

Left atrial (LA) remodeling is a feature of the full spectrum of heart failure (HF) and LA structural remodeling (fibrosis) will contribute to diminished ventricular contractile function and risk of atrial fibrillation. Whilst the fibrotic potential of the LA in HF has been documented, the mechanism by which this occurs, and the role of other matrix proteins is less well understood.HF was induced in female sheep by rapid ventricular pacing. LA dilatation was present in symptomatic animals as measured by echocardiography. Paraffin embedded tissue sections from the left auricle were stained with picro‐sirius red or Millers stain for quantification of collagen and elastin, respectively. Microscopy revealed both elastic, and collagenous components and in HF, collagen:elastin ratio was increased. Gelatinase activity was measured by zymography and protein levels of the elastin‐degrading MMP ‐3, TIMPs 1–4 and secreted protein acidic and rich in cysteine (SPARC) were measured by immunoblotting. MMP‐2 activity, MMP‐3 and SPARC proteins were increased after rapid pacing, whereas levels TIMP‐1 were decreased.Both collagen and elastin networks are altered in the ovine LA in HF which is likely to contribute towards a stiffer, less compliant phenotype. Changes to different MMP profiles in failing atria may provide a mechanism for this atrial extracellular matrix remodeling.Work was funded by the BHF.
Endothelium dependent vasodilation in young, obese adults: contribution of NOS
Authors: Lee Peltonen Garrett , Johansson Rebecca E , Harrell John W , Limberg Jacqueline K , Crain Meghan K. , Sebranek Joshua J , Walker Benjamin J , Marlowe Eldridge W , Schrage William G 
Published: June 2021

Endothelium dependent vasodilation (EDD) is impaired in older, obese adults. However, it remains unknown whether this impairment exists in young, obese adults. We hypothesized that young, obese adults would exhibit attenuated EDD and altered nitric oxide (NO) production. In 10 young, lean (age: 27±2 yrs; BMI: 23±1 kg/m2) and 7 young, obese (23±2 yrs; 38±4 kg/m2) adults forearm EDD was assessed with infusion of acetylcholine (ACH) into the brachial artery. Contribution of NO to EDD was determined by simultaneous infusion of LNMMA and ACH. Smooth muscle responses to NO were tested with nitroprusside (NTP). Forearm blood flow (FBF) was measured with Doppler ultrasound and normalized for mean arterial pressure (MAP) by calculating forearm vascular conductance (FVC =FBF/MAP). ACH infusion increased FVC (p<0.01). FVC was greater in obese versus lean adults expressed as either an absolute value (207 vs. 130 ml min−1 mmHG−1; p<0.01) or change from baseline (165 vs. 90; p<0.01). NOS inhibition decreased ACH mediated EDD (p=0.02) equally in lean and obese subjects. FBF responses to NTP were similar between groups. In conclusion, our data suggest that young obese adults exhibit greater EDD, but this is not due to altered NOS function.Support: NIH R01 HL105820.
Non‐Uniform Age‐Related Decrements in Regional Sweating and Skin Blood Flow
Authors: Smith Caroline J. , Alexander Lacy M. , Kenney W. Larry 
Published: June 2021

Aging is associated with attenuated thermoregulatory effector function which varies regionally over the body. Our aim was to examine age‐related alterations in the relation between regional sweating (RSR) and skin blood flow (SkBF) in response to thermal and pharmacological stimuli. Four microdialysis (MD) fibers were placed in the ventral forearm, abdomen, thigh, and lower back of 8 healthy older (O, 64 ± 2 yrs) and 9 young (Y, 23 ± 2 yrs) men and women matched for anthropometric characteristics and VO2max. RSR and SkBF (laser‐Doppler flux; LDF) were measured over each MD site during whole body heating (WBH; Δ1°C oral temperature) and acetylcholine dose response protocols (ACh 1×10−7–0.1M). During WBH RSRs were attenuated (p<0.001) and onset thresholds were delayed at all sites (p<0.05) in the O. SkBF was also attenuated with age (p<0.001) with few differences in onset (Y vs. O back p<0.05). Within groups, RSR (p<0.001) but not SkBF varied among sites. Cholinergic sensitivity was similar between groups for RSR but varied for SkBF (arm 1.0–10mM P<0.05; abdomen p<0.05). RSR did not differ among sites but SkBF varied in the O (p<0.05). Together these data suggest regional age‐related decrements in heat‐activated sweat gland function but not cholinergic sensitivity. Site‐specific difference in sweating tend to disappear with aging.Supported by NIH RO1‐ AG007004‐22 (W.L.K.) and ACSM Foundation Research Endowment 2012 (C.J.S).
A novel look at KIR channels and potassium in human skin
Authors: Francisco Michael A , Fujii Naoto , Minson Christopher T , Brunt Vienna E 
Published: June 2021

Tetraethylammonium (TEA) abolishes a large portion of the vasodilation observed with both cutaneous thermal and reactive hyperemia by blocking calcium‐sensitive potassium (KCa) channels. Some studies have shown effects of TEA on other potassium channels such as inward‐rectifying potassium (KIR) channels, which are activated by increases in extracellular K+ and blocked by barium (Ba2+). Our primary goal was to test the specificity of TEA to KCa channels by ensuring TEA has no effect on KIR‐mediated vasodilation to KCl. In doing so, we also observed novel insights into the roles of KIR channels and K+, which have not been studied in skin. The following drugs were infused via microdialysis: 1) Control; 2) 50mM TEA; 3) 100μM barium chloride (BaCl2; KIR channel blocker to verify the effects of KCl). KCl was infused for 2 min at each site at 1mM, 10mM, and 100mM doses. Dilation was characterized as Δ peak from baseline, and presented as % maximal cutaneous vascular conductance (CVC). Dilation at the control site (1mM: 10.3±4.8%, 10mM: 10.2±4.2%,100mM: 11.9±4.4%) indicated 1mM KCl is sufficient to achieve maximal activation of KIR channels, which is only ~ 10% of max. All dilation to KCl can be blocked with 100μM BaCl2 (1mM KCl: 4.0±2.1%, 10mM KCl: 0.8±0.7%). Furthermore, TEA had no effect on KCl‐mediated dilation (1mM KCl: 10.8±4.6%, 10mM: 11.9±5.6%), confirming that TEA is specific to KCa channels.Supported by NIH Grant HL081671
Rett Syndrome mutation MeCP2 T158A affects hypoxic ventilatory response in mice
Authors: Bissonnette John M , Knopp Sharon J , Zhou Zhaolan 
Published: June 2021

Rett syndrome (RTT), whose phenotype includes respiratory disorders, is caused by loss‐of‐function mutations in methyl‐CpG‐binding protein 2 (MeCP2). Mouse models of the syndrome that have been generated by deletion of Mecp2 have an altered ventilatory response to acute hypoxia (HVR) characterized by a minute ventilation (VE) that exceeds wild type (WT) and that persists in the early recovery period. Such large deletions, however, account for only ~10% of cases. Here we determine if mice with a common single point mutation retain this respiratory pattern. Knockin mice that carry a RTT‐associated threonine to alanine mutation at residue 158 (T158A) show RTT‐like behavioral phenotypes similar to Mecp2‐null mice (Nature Neuroscience 15:274,2011). Experiments were performed in heterozygous T158A female mice at 9 months of age. Baseline respiratory frequency, tidal volume and minute ventilation in T158A animals was similar to WT. Compared to WT littermates relative VE of T158A at 1 min of 8% O2 was twice as large. WT mice showed the expected post‐hypoxia frequency decline (224±9.5 to 203±12 bpm) while T158A had a sustained tachypnea (203±10 to 219±14.5). HVR in mice with a T158A mutation is similar to that with a null mutation of MeCP2.Support: IRSF, RSRT, NewLife Foundation (JMB); NIH, IRSF (ZZ)
Role of vascular dysfunction in prostate tumor perfusion during exercise
Authors: McCullough Danielle J. , Siemann Dietmar W , Behnke Bradley J 
Published: June 2021

During exercise, blood flow to inactive tissues is reduced through changes in vascular tone elicited largely by the autonomic nervous system. However, in tumors the reduced innervation of feed arteries and possibly blunted adrenergic vasoconstriction may lead to an increased tumor perfusion during exercise. We used control (CON; n=16) and prostate tumor bearing (TB; n=14) Copenhagen rats to test the hypothesis that α‐adrenergic (via norepinephrine; NE) and myogenic vasoconstrictor responses are diminished in the prostatic tumor feed arteries (PTA), resulting in an increased tumor perfusion during exercise. Dunning R‐3327 MatLyLu tumor cells (104) were injected into the ventral prostates of rats. PTA and prostate arteries (CON) were studied in vitro and exposed to cumulative additions of NE (10−9to 10−4M) and increases in intraluminal pressure (myogenic response; 0 to 135 cmH2O). In vivo quantification of perfused tumor vessels during rest and acute exercise (treadmill; 5 min) was determined using Hoechst‐33342 staining. Both α‐adrenergic (7 ± 6% vs. 88 ± 2%, p<0.05) and myogenic vasoconstriction were blunted in PTA versus CON, while the number of PTA perfused increased ~113% with exercise. These data suggest that dysfunction in the PTA results in an inability to augment vascular resistance during exercise, resulting in an enhanced tumor perfusion.Supp.: NIH (AG‐31317) & Florida Biomed. Res. Prog. (1BN‐02).
A fetal mouse lung slice model for molecular live cell imaging of the pulmonary neuroepithelial body microenvironment
Authors: Schnorbusch Kathy , Brouns Inge , Lembrechts Robrecht , Pintelon Isabel , Timmermans Jean‐Pierre , Adriaensen Dirk 
Published: June 2021

The prominent presence of differentiated neuroepithelial bodies (NEBs) from early embryonic development on, with the highest density in the perinatal period, reflects important prenatal functions and involvement in the transition from fetal to neonatal life. We therefore adapted our established ex vivo live cell imaging lung slice model to allow functional studies in fetal mouse lungs.Using Fluo‐4, changes in [Ca2+]i could be monitored, revealing that ATP causes a [Ca2+]i rise in fetal airway epithelial cells. Additional identification of prenatal NEBs with the vital dye 4‐Di‐2‐ASP, showed that extracellular high K+ evoked a reversible [Ca2+]i increase in fetal NEB cells. Fixed lung slices of prenatal mice revealed immunostaining for CGRP in NEBs, and a P2X3 ATP receptor‐expressing population of NEB‐associated nerve terminals, highlighting the possibility to directly link physiology to neurochemistry in this model. Since slices of fetal GAD67‐GFP knock‐in mice show selective GFP fluorescence in NEB cells, use of these animals will definitely improve physiological studies of NEBs.The presented fetal mouse lung slice models offer excellent possibilities for molecular live cell imaging to further unravel the functional significance of the NEB microenvironment during the pre‐ and perinatal period.Grants: IWT (SB 81162); FWO (G.0589.11), Hercules Foundation (AUAH‐09–001); UA (GOA BOF 2007; KP BOF 2011)
Angiopoietin like‐2 knock‐down improves the lipid profile of high‐fat diet‐fed mice and maintains vascular endothelial function
Authors: Yu Carol , Thorin Eric 
Published: June 2021

Angiopoietin like‐2 (angptl2), a member of the angiopoietin‐like protein family, can contribute to insulin resistance in obesity (Tabata 2009). However, angptl2 involvement in lipid profiling and vascular endothelial function remain largely unknown.ObjectiveAn angptl2 knock‐down (KD) mouse was used to study the role of angptl2 in lipid handling and endothelial function in the femoral artery.Methods/results3 month‐old wild‐type (WT) and KD mice were fed a regular diet (RD) or high‐fat diet (HFD) until 6 months of age. WT and KD mice displayed similar lipid profiles under the RD. While total cholesterol and high‐density lipoprotein (HDL) levels increased similarly in WT and KD mice after a HFD, low‐density lipoprotein (LDL) levels increased 2.7‐fold in WT and only 1.9‐fold in KD so that total cholesterol‐to‐HDL and LDL‐to‐HDL ratios increased significantly (P<0.05) only in WT but not in KD following HFD. Under a RD, KD mice displayed improved endothelial function as measured by the EC50 of the acetylcholine‐induced dose‐response curve. Although this difference in sensitivity between the two strains was lost after a HFD, contribution by nitric oxide (NO) was maintained in KD but not in WT.ConclusionAngptl2 knock‐down in mice may improve lipid handling when challenged with a HFD, and lead to maintenance of endothelial function, specifically NO contribution to vasorelaxation. Supported by CIHR 14496 and NSERC.
Systemic oxidative stress in older adults: Do peripheral blood mononuclear cells contribute?
Authors: Schanzle Jennifer C , Deo Shekhar H , Fadel Paul J 
Published: June 2021

Although it is well known that systemic oxidative stress increases with age, the sources and mechanisms contributing to aging induced increase in oxidative stress remain unclear. Recent findings in animals indicate that peripheral blood mononuclear cells (PBMCs) are a major source of systemic oxidative stress via stimulation of the angiotensin II type 1 receptor (AT1R)‐NADPH oxidase pathway. Thus, to better understand this pathway and its potential contribution to increased oxidative stress with age, PBMCs were isolated from whole blood in healthy recreationally active older (61 ± 2 years, n=5) and younger men (25 ± 2 years, n=7). Intracellular superoxide production was measured using dihydroethidium fluorescence and NADPH oxidase subunits (gp91phox, p22phox, and p67phox) and superoxide dismutase 1 and 2 (SOD1 and SOD2) mRNA expression was measured using real time RT‐PCR. Interestingly, intracellular superoxide production was similar between groups (2 ± 0.4 older vs. 2 ± 0.3 young, Relative Fluorescence Units; P>;0.05). Likewise, gp91phox and p22phox were not different between groups, whereas p67phox was actually significantly lower in older subjects. Aging did not influence SOD2 mRNA expression, while SOD1 expression was lower in older subjects. These preliminary findings suggest that PBMCs may not be a primary source of systemic oxidative stress in healthy older individuals.Supported by NIH Grant R01 HL093167
The New Mode to Neurohumoral Regulation in Respiratory and Circulatory Systems
Authors: Sun Xing‐Guo 
Published: June 2021

We defined the sophisticated organic whole by placing oxygen (along with CO2 and [H+] Trinity) as the core. The regulation through integrative nervous system is still unclear. In order for us to easily comprehend the working mode of respiratory and circulatory regulations, we use an analogy of ¡°sound system regulation mode¡±: 1. The wave signal generated by the circulating blood in the circulatory system due to pulmonary ventilation is compared to the speech acoustic signals produced by person. 2. Multiple peripheral chemoreceptors and baroreceptors are compared to the sonic microphones that sense sound waves; they collect and upload distinct signals. 3. The central nervous system is equivalent to the volume amplifier control system. 4. The central chemoreceptors act as a volume‐adjusting knob; it balances the central incoming/outgoing integration. 5. The respiratory muscle and thorax lung jointly play the role of a speaker.This concept explains why we can stably maintain our respiration by breath‐by‐breath pattern via respiratory muscles contraction/diastole conversion. Similarly, our circulation can be maintain stable by beat‐by‐beat pattern.
The combined effects of Anastrozole and Testosterone or Trenbolone on Prostate and Levator Ani‐Bulbo Cavernosus Mass
Authors: Beck Darren Thomas , Yarrow Joshua F , McCoy Sean C , Beggs Luke A , Ye Fan , Balaez Alexander , Combs Sarah M , Miller Julie R , Conover Christine F , Borst Stephen E 
Published: June 2021

Our purpose was to determine the role of the aromatase enzyme in mediating the myotrophic and prostate enlarging effects of androgens. 10 month old Fisher 344 rats received Sham surgery or orchiectomy (ORX). One week following surgery animals were implanted with motorized micro‐infusion pumps to disperse anastrozole (ANA; aromatase inhibitor) or vehicle at a rate of 2.0 μl/hour. Animals received once weekly IM testosterone enanthate (TE; 7.0mg/week), trenbolone enanthate (TREN; 1.0mg/week), or vehicle. 28 days following pump implantation animals were sacrificed and the prostate and levator ani‐bulbocavernosus (LABC) muscle were excised.

Group (n=3)

Prostate (g)
LABC (g)

SHAM
(a)
0.29±0.064 c
0.88±0.033 b,c,d,e,f,g

ORX
(b)
0.07±0.014 d,e
0.45±0.004 d,e,f,g

ORX+ANA
(c)
0.06±0.003 a,d,e
0.48±0.025 d,e,f,g

ORX+TE
(d)
0.31±0.037 b,c
1.20±0.034 a,b,c

ORX+TE+ANA
(e)
0.31±0.074 b,c
1.22±0.046 a,b,c

ORX+TREN
(f)
0.15±0.064
1.19±0.035 a,b,c

ORX+TREN+ANA
(g)
0.18±0.033
1.19±0.013 a,b,c

Values are mean±SEM. Significance values are reported from one‐way ANOVA and Tukey posthoc group comparison; letters indicate p<0.05 vs. group.

Our findings suggest that estradiol is not required for androgen mediated prostate enlargement. Further, inhibiting the aromatase enzyme did not blunt the myotrophic effects of androgens.Supported by VA Merit Award to SEB and VA Geriatrics Fellowship to DTB.