bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mathematical Model of Plasma Membrane Electrophysiology of a Brain Capillary Pericyte: Investigating Pericyte Contribution to the Electrical Properties of the Capillary Network
Authors: Mirza Asad M. , Moshkforoush Arash , Giles Wayne R. , Tsoukias Nikolaos 
Published: June 2021

IntroductionPericyte cells (PCs) are specialized cells found primarily on the abluminal surface of capillary blood vessels alongside endothelial cells (ECs). They play a role in angiogenesis, formation of the blood‐brain barrier, as well as in the regulation of blood flow. Due to their contractile nature, PCs can modulate capillary diameter and perfusion, however, little is known regarding their contribution to the electrical properties of the capillary network. Furthermore, recent studies show that capillaries can sense neural activity in the brain and transmit electrical signals to upstream feeding arterioles and arteries to match blood supply to local demand. Although passive electrotonic spread underlies signal propagation along the endothelium in larger vessels, evidence for amplification of transmitted signals and preferential upstream propagation have been presented in vessels as branching order increases. We use mathematical modeling to test under what conditions a PC can affect the electrical properties of the capillary network and whether it can act as a sink or an amplifier of conducted hyperpolarization.MethodsA PC and an EC model incorporate the dynamic behavior of known plasma membrane currents, release and uptake of Ca2+ by intracellular stores and dynamic tracking of ionic (Ca2+, K+, Na+, and Cl−) concentrations in the cytosol (Fig. 1). The PC is electrically coupled to capillary ECs through gap junctions and a multicellular model of a capillary network is created. Electrical signal attenuation is examined following hyperpolarizing stimuli at capillary ends in the presence as well as absence of PCs at network bifurcations.ResultsCell models predict physiological resting membrane potential and ionic concentrations. Model predictions were compared against experimental responses to agonist stimulation and K+ challenge for validation. Simulations show that a sufficient inwardly rectifying K+, Kir, channel current density may allow PCs to amplify conducted hyperpolarization. Increased coupling between a PC with the parent relative to the daughter capillaries at a bifurcation may allow preferential conduction of an electrical signal upstream the vascular network.ConclusionA detailed model of a brain capillary pericyte was developed and validated against experimental data. Model simulations suggest that with sufficient Kir density, pericytes can amplify conducted hyperpolarization and regulate the distance and direction of propagating vasodilation and thus blood flow distribution in the vascular network.Support or Funding InformationThis work was supported by the Ronald E. McNair Post‐Baccalaureate Achievement Program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Excessive shear stress sensing on the arterial endothelium initiates cerebral aneurysm formation
Authors: Fukuda Miyuki , Fukuda Shunichi , Ando Joji , Yamamoto Kimiko , Ito Yuki , Inoue Takayuki , Tsukahara Tetsuya , Asahara Noriko , Hasegawa Koji , Shimazu Akira 
Published: June 2021

Although rupture of cerebral aneurysms is a major cause of life‐threatening subarachnoid hemorrhage, there are no effective therapeutic drugs for the treatment of aneurysms, partly because the pathogenesis of the aneurysm remains unresolved. We hypothesize that shear stress‐related hemodynamics initiates cerebral aneurysm formation. To test this hypothesis, we examined here whether disruption or inhibition of the endothelial shear stress sensor, P2X4 purinoceptor, has any influence on expressions of known contributors to aneurysm formation or not.P2X4 purinoceptor deficient (P2X4 KO) mice and Sprague‐Dawley rats were subjected to cerebral aneurysm‐generating surgery with ligation of unilateral common carotid artery and renal hypertension. P2X4 purinoceptor inhibitor, paroxetine (8 mg/kg/day) was administered to rats after the surgery. The incidence of aneurysm formation was examined with light microscopy, and expressions of contributors to aneurysm formation using a quantitative real‐time PCR analysis and immunohistochemical examinations.The frequency of aneurysm induction in P2X4 KO mice was significantly lower than wild‐type mice (p=0.018). In addition, paroxetine significantly attenuated the incidence of induced aneurysms in rats after aneurysm‐generating surgery (p=0.031). Expression levels of inflammatory contributors to aneurysm formation, COX‐2, TNFα, MCP‐1, IL1β, and iNOS, were significantly increased in rats after aneurysm‐inducing surgery than control non‐operated animals by a quantitative real‐time PCR analysis. Paroxetine significantly reduced the expression levels of all the contributors.These data suggest that shear sensing on the arterial endothelium initiates chronic inflammation in the arterial wall during cerebral aneurysm formation. Because paroxetine has been used for human as an antidepressant, clinical use of this P2X4 purinoceptor inhibitor is expected as a novel therapy for cerebral aneurysms.Support or Funding InformationThis work is supported by Japan Agency for Medical Research and development, AMED and JSPS KAKENHI Grant Number JP15K10323.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oral Metoprolol Attenuates Dilation of Leptomeningeal Collateral Arteries after Middle Cerebral Artery Occlusion and Increases Infarct Volume in Sprague Dawley Rats
Authors: Henry David S. , McClenahan Samantha J. , Rusch Nancy J. , Rhee Sung W. 
Published: June 2021

BackgroundBeta‐adrenergic receptor antagonists, or beta blockers (BBs), have long been a mainstay in the treatment of hypertension, heart failure, and angina. In 2014, the Eighth Joint National Committee removed BBs from the list of recommended first‐line hypertension therapies, citing an increased incidence of stroke among patients treated with BBs compared to other antihypertensive medications. However, in 2015, more than 72 million prescriptions of this drug class were filled in the United States. The mechanism behind worse stroke outcomes in BB‐treated patients is unknown. Leptomeningeal collateral arteries (LCAs) connect adjacent arterial trees of the cerebral circulation, and after ischemic stroke, provide an alternative pathway for blood flow to the affected cortical tissue. We hypothesize that beta‐adrenergic receptor‐mediated dilation of LCAs is an important part of this protective mechanism during ischemic stroke and that BBs attenuate this dilation, leading to worse stroke outcomes.Methods and ResultsLCAs dilated in a concentration‐dependent manner to topical application of the beta‐adrenergic receptor agonist isoproterenol in cranial window preparations in Sprague Dawley (SD) rats. Isolated, pressurized LCAs dilated in response to isoproterenol ex vivo, and this dilation was attenuated by the beta1‐selective blocker CGP20712 (30 nM). LCAs acutely dilated after middle cerebral artery occlusion (MCAO) in SD rats. The dilation of LCAs after MCAO was reduced in rats suffused with topical CGP20712 (100 nM) or gavaged with oral metoprolol (30 mg/kg), the most frequently prescribed BB. Similarly, blood flow through LCAs post‐MCAO was reduced in rats gavaged with metoprolol compared to control rats, as visualized by laser speckle contrast imaging. Finally, infarct volume, as measured by MRI one day post‐MCAO surgery, was larger in rats gavaged with metoprolol compared to control. Interestingly, the heart rate and systemic blood pressure measured by biotelemetry for 6 hours following MCAO surgery were not different in rats gavaged with metoprolol and water.ConclusionsOur study suggests that BBs may promote worse stroke outcomes by disrupting beta‐adrenergic receptor‐mediated dilation of LCAs.Support or Funding InformationSupported by NIH R01 HL097107, American Heart Association 17GRNT33670970, and Institutional Hornick and Fund‐to‐Cure‐Stroke grantsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebral Blood Flow Characteristics Responses Following Acute Aerobic Exercise in Individuals with and without Down Syndrome
Authors: Wee SANG OUK , Schroeder Elizabeth C. , Grigoriadis Georgios , Bunsawat Kanokwan , Rosenberg Alexander J. , Griffith Garett , Baynard Tracy , Fernhall Bo 
Published: June 2021

Individuals with Down Syndrome (DS) commonly experience low to moderate levels of cognitive impairment and are at a high risk of developing dementia and Alzheimer's diseases (AD). Reduced cerebral blood flow (CBF) and altered CBF characteristics have been observed in the aging population without DS and has shown to have detrimental effects on cerebral microvasculature, which may increase the risk of developing dementia and AD. However, differences in CBF and its characteristics between individuals with and without DS and its response to exercise have not been studied.PurposeTo examine the differences in CBF and its characteristics following a 20‐minute bout of moderate intensity walking in individuals with and without DS.MethodsThirty‐eight young (DS=19, Age=25 yrs) individuals with and without DS participated in this study. Changes in mean middle cerebral artery velocity (mMCAv), mMCAv characteristics (pulsatility index (PI), resistance index (RI)) and hemodynamic variables were measured before, immediately post and 30‐minute post exericse.ResultsBaseline hemodynamics, systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), heart rate (HR) and mMCAv were not different between the DS and control group (p>0.05 for all). Neither group showed changes in mMCAv after moderate intensity treadmill walking exercise (p>0.05). However, the DS group exhibited significantly higher PI and RI at all time points when compared to controls (p<0.05 for both).ConclusionsOur results demonstrate that CBF was not altered in individuals with DS at rest and following moderate intensity exercise and was not different from that of controls. However, higher PI and RI in DS group may be associated with reduced distal cerebral perfusion and microvascular damage in individuals with DS.

DS (N = 19)
Control (N = 19)

Baseline
Immediate post EX
30‐minute post EX
Baseline
Immediate post EX
30‐minute post EX

SBP (mmHg)
122±14
126±11*
121±13
120±10
130±12*
121±11

DBP (mmHg)
69±9
75±8*
70±9
72±6
81±8*
74±9

MAP (mmHg)
93±10
98±8*
94±9
94±7
103±7*
96±8

mMCAv (cm/s)
64.3±14.9
62.8±13.9
60.8±14.6
69.4±13.1
69.8±14.8
69.6±14.1

PI‡
0.97±0.14
1.04±0.19
1.02±0.14
0.87±0.12
0.89±0.15
0.86±0.14

RI‡
0.60±0.05
0.61±0.06
0.61±0.05
0.56±0.05
0.56±0.05
0.55±0.05

Significant group difference,
Significant time difference from the baseline.
Mean ± SD, Significance level, p < 0.05

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sodium Nitroglycerin Induces Cerebrovascular Vasodilation in Patients with Ischemic Heart Disease
Authors: Schulz Jenna M. , Al‐Khazraji Baraa K. , Vording Jennifer L. , Shoemaker J Kevin 
Published: June 2021

Aging patients with ischemic heart disease (IHD) have impaired cerebrovascular vasodilation in response to hypercapnia, but whether this is due to endothelial dysfunction or impairment in the vascular smooth muscle remains unknown. Further, despite being a standard drug given to patients with cardiovascular disease, the role of an exogenous nitric oxide donor (sodium nitroglycerin – NTG, which acts independently of the endothelium) in the cerebrovasculature in these patients is not known. This study tested the hypothesis that age and IHD impair nitric oxide‐mediated dilation (sodium nitric oxide, 0.4 mg spray) of the nine larger cerebral arteries in the Circle of Willis (3 Tesla MRI), as well as mean flow velocity [transcranial Doppler ultrasound; right middle cerebral artery (MCA)] and calculated MCA cerebral blood flow. These measures were made in groups of IHD (n=10, 49–77 years), older controls (CTL; n=5, 51–78 years) and young healthy (YH; n=10, 20–26 years) individuals. Compared to baseline, right MCA velocity [V (cm/s)] decreased similarly in all three groups [ΔIHD: −5.8 ± 5.0 cm/s; ΔCTL: −5.8 ± 3.2 cm/s; ΔYH: −6.3 ± 4.4: all p<0.05 versus baseline; mean ± S.D.]. However, a main effect of drug indicated that NTG induced artery dilation in all six basal and the three extracranial arteries [average range of cross sectional area values for all vessels provided here: BL: 3.3 – 16.5 mm2; NTG: 3.9 – 17.9 mm2, p<0.05, mean], and this dilation was similar across all 3 groups [e.g. right MCA CSA – ΔIHD: 1.3 ± 1.4 mm2; ΔCTL: 0.7 ± 1.2 mm2; ΔYH: 1.3 ± 0.9 mm2, p>0.05 versus baseline; mean ± S.D.]. As a result, NTG exerted no change in MCA blood flow versus baseline. These results demonstrate that age and IHD have little impact on vascular smooth muscle responses to exogenous nitric oxide.Support or Funding InformationSupported by Canadian Institute for Health Research (201503MOP‐342412‐MOV‐CEEA)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of altered physical activity on vascular function in older adults: A divergent impact on the conduit and microvascular systems
Authors: Broxterman Ryan M. , Trinity Joel D. , Gifford Jayson R. , Park Soung Hun , Shields Katherine L. , Drummond Micah J. , Richardson Russell S. 
Published: June 2021

Aging is associated with a progressive decline in physiological and functional reserve capacity in humans. The rate of this decline is accelerated by periods of reduced activity. Prolonged reductions in physical activity (i.e. weeks) are commonly incurred with age‐related insults (i.e., hospitalization, injury, illness) in older adults. The effect of these periods of reduced activity on vascular function reserve remains to be determined. Any detrimental effects of this reduced activity on vascular function are clinically relevant, as this would pose an increased risk for adverse cardiovascular events. Furthermore, it remains to be determined if any detrimental effect on vascular function incurred during prolonged reduced activity is reversible with resumption of normal activity. Therefore, the purpose of the current study was to investigate the effects of prolonged reductions in physical activity, followed by a return to normal activity, on leg vascular function in older adults. Popliteal artery flow‐mediated dilation (FMD) and reactive hyperemia were measured at baseline, following 14 days of reduced activity (i.e. 70% reduction in steps per day), and 14 days after returning to normal activity in 5 healthy older subjects (2 men and 3 women, age: 70 ± 8 yrs, stature: 164 ± 13 cm; body mass, 69 ± 10 kg). The steps per day during the reduced activity period (3,212 ± 1,673 steps) were significantly lower than both baseline (11,007 ± 2,417 steps) and return to normal activity (10,068 ± 1,357 steps), while baseline and return to normal activity were not significantly different (p = 0.29). Popliteal artery FMD was significantly attenuated following reduced activity and returned to baseline after 2 weeks of normal activity (Figure 1A). There were no significant differences between conditions in popliteal artery shear rate (p = 0.43). The popliteal artery reactive hyperemia was not significantly different between conditions (p = 0.70, Figure 1B). Therefore, a prolonged, 14 day, alteration in physical activity in older adults directly influences leg conduit artery vascular function (i.e. FMD), while leg microvascular function (i.e. reactive hyperemia) remains unaltered. These results document the influence of alterations in physical activity on cardiovascular health in older adults, but also highlight a divergent impact on the conduit and microvascular systemsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired ATP Release in Individuals with Type 2 Diabetes Assessed by the Intravascular Microdialysis Technique
Authors: Mortensen Stefan P. , Groen Martin B. , Knudsen Trine A. , Finsen Stine , Pedersen Bente K. , Hellsten Ylva 
Published: June 2021

BackgroundATP is a potent vasodilator in plasma and is released from erythrocytes upon deoxygenation. In vitro studies suggest that individuals with type 2 diabetes (T2D) have an impaired ATP release when exposed to low oxygen tension and a reduced capability to induce vasodilation. We sought to examine if patients with T2D have reduced plasma ATP levels during resting conditions, hypoxia and during increased metabolic demand compared to healthy individuals.MethodsWe measured femoral arterial and venous plasma ATP with the intravascular microdialysis technique during normoxia, hypoxia and one‐legged knee‐extensor exercise in 9 individuals with T2D and 8 healthy controls. Moreover, we infused ACh, SNP and ATP to test vascular function.ResultsPatients with T2D had an impaired increase in venous plasma [ATP] during exercise in parallel with a reduced leg blood flow and vascular conductance compared to the healthy controls. Arterial plasma [ATP] increased in both groups during exercise, but tended to be higher in the healthy controls (P=0.05–0.07). During systemic hypoxia, venous plasma [ATP] increased in both groups, but the increase was higher in the healthy controls. Leg vascular conductance was lower during ATP and ACh infusion in the patients with T2D compared to the healthy controls.ConclusionsThese findings demonstrate that patients with T2D have impaired ATP release during exercise and hypoxia compared to healthy humans. Moreover, T2D have a reduced vasodilatory response to infused ATP. These impairments in the ATP are likely to contribute to the reduced tissue perfusion in T2D.Support or Funding InformationThis study was funded by the Capital Region of Denmark.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Estrogen Does Not Augment the β2 ‐ Adrenergic Receptor Mediated Vasodilation in Postmenopausal Women
Authors: Ranadive Sushant Mohan , Dillon Gabrielle A. , Joyner Michael 
Published: June 2021

IntroductionAcute estrogen infusion augments β2 ‐adrenergic receptor responsiveness in premenopausal women. This suggests an influential role of estrogen in controlling the vasodilator responsiveness via β2 ‐adrenergic receptors in premenopausal women. Postmenopausal women present with a reduced β2 ‐adrenergic receptor responsiveness as compared to premenopausal women. This divergent finding in β2 ‐adrenergic receptor responsiveness could be due to loss of endogenous estrogen postmenopause.ObjectiveHence, the objective of the study was to compare the β2 ‐adrenergic vasodilator responses with and without estrogen in postmenopausal women. We hypothesized that the vasodilator effects during endothelial dependent, independent and during β2 ‐adrenergic agonist infusion would be significantly greater with acute, local estrogen administration.MethodsVenous occlusion plethysmography was used to measure forearm blood flow (FBF) in 8 older (age = 59 ± 1 years) healthy, non‐obese (BMI = 23 ± 1 kg/m2) women. FBF was measured at baseline and during an intra‐arterial infusion of acetylecholine (ACH) at 1.0, 2.0, 4.0, and 8.0 μg/100 ml tissue/min, sodium nitroprusside (NTP) at 0.25, 0.5, 1.0 and 2.0 ug/100 ml tissue/min and terbutaline (β2 agonist) at 0.1, 0.5, 1.0, 2.0 μg/100 ml tissue/min before (with dextrose co‐infusion) and during acute, local intra‐arterial infusion of estrogen (20 ηg/mL at 1 mL/min). Forearm vascular conductance (FVC) was calculated as FBF divided by mean arterial pressure. Area under the curve (AUC) was calculated for the absolute FVC and percent baseline FVC of ACH, NTP and terbutaline.ResultsThere were no significant differences in FVC with estrogen infusion as compared to control during ACH, NTP and all terbutaline doses except dose 2 of ACH (Table 1). The AUC are not significantly different during estrogen (p>0.05) as compared to control for ACH, NTP and terbutaline (figure 1).ConclusionsThese data suggest that acute administration of estrogen, which corresponds to the endogenous levels of estrogen seen in premenopausal women during mid‐cycle, does not augment the β2 ‐adrenergic vasodilator responses in postmenopausal women. Additionally, these data suggest that estrogen infusion does not increase the endothelial dependent and independent vasodilatory capacity in postmenopausal women.Support or Funding InformationHL83947 (MJJ) and Mayo Clinic Women's Health Scholarship (K12 HD065987).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Activation of Bradykinin‐Sensitive Pericardial Afferents Increases Systemic Venous Tone and Cardiac Output
Authors: Martin Doug , Reihe Casey 
Published: June 2021

The venous system plays a critical role in blood pressure regulation by controlling venous return, cardiac filling, and cardiac output. Sympathetic drive is a major controller of venous function. However, outside of the arterial baroreflex, the mechanisms that regulate sympathetic drive to veins remain poorly defined in both physiological and disease conditions. The heart itself has an important sensory function via a variety of cardiac receptors that modulate cardiovascular function by neural and humoral reflexes. Bradykinin‐sensitive sympathetic afferent nerves from the heart can trigger marked increases in efferent sympathetic nerve activity to some cardiovascular target organs such as the kidney. This work tested the hypothesis that the activation of bradykinin‐sensitive cardiac afferents increases venous tone and cardiac output.Sprague Dawley rats were anesthetized with a cocktail of alpha chloralose (80 mg/kg) and urethane (800 mg/kg). Catheters were placed in the femoral artery and vein to record arterial and venous blood pressures. A PE 10 catheter was placed in the pericardial space for the injection of bradykinin (BK), an agent known to stimulate cardiac sympathetic afferents. In some rats, a balloon tipped catheter was placed in the right atrium to allow transient arrest of cardiac pumping for the estimation of mean circulatory filling pressure (MCFP), an estimate of systemic venous tone. In other rats, an electromagnetic flow probe was placed on the aortic arch for the direct measurement of cardiac output.In rats instrumented for the measurement of venous tone, pericardial injections of BK (0.4–20 μg/kg) were associated with dose‐related increases in mean arterial pressure (9±6 to 27±6 mm Hg) and MCFP (0.6±0.2 to 1.6±0.4 mm Hg). These responses were largely attenuated after ganglionic blockade. In rats instrumented for the measurement of cardiac output, pericardial injection of BK (10 μg/kg) increased mean arterial pressure (23±3 mm Hg) and cardiac output (16±2 ml/min).We interpret these data to indicate that activation of bradykinin‐sensitive pericardial afferents increases venous tone sufficiently to increase cardiac filling and cardiac output.Support or Funding InformationSupported by NIH R01 HL136741‐01 and the Basic Biomedical Sciences program of the Sanford School of Medicine, University of South Dakota.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.