bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vagally mediated low pressure baroreflex evokes biphasic changes in sympathetic nerve activity and resets the arterial baroreflex (1169.12)
Authors: Oga Yasuhiro , Kishi Takuya , Saku Keita , Kakino Takamori , Ikeda Masataka , Nishizaki Akiko , Kuwabara Yukimitsu , Ide Tomomi , Sunagawa Kenji 
Published: June 2021

Background: Although volume loading activates the low pressure baroreflex (LBR), its quantitative impact on sympathetic nerve activity (SNA) and arterial baroreflex (ABR) remains unknown. The aim of this study is to clarify how the LBR affects SNA and ABR.Methods/Results: In 10 anesthetized rats, we isolated carotid sinuses and controlled carotid sinus pressure (CSP). We infused dextran to activate LBR. We measured central venous pressure (CVP) and SNA. We fixed CSP at 90mmHg to abolish ABR. We infused dextran of 5% blood volume stepwise with or without vagotomy. In the low CVP range (2.6±0.8 to 4.5±0.7mmHg), volume loading increased SNA as much as 64.8±19.5% from the baseline, while further volume loading in the high CVP range (4.5±0.7 to 7.0±0.8 mmHg) returned SNA to the baseline level. Bilateral vagotomy totally abolished those changes in SNA. To assess the impact of LBR on the ABR central system, we changed CSP stepwise from 60 to 160 mmHg at the normal volume, mild volume loading and high volume loading while recording SNA responses. Mild volume loading (CVP: 3.8±0.6 mmHg) increased SNA by resetting the CSP‐SNA relation upward (+45.2%), while, high volume loading (CVP: 6.0±0.3 mmHg) decreased SNA by resetting the CSP‐SNA relation to the baseline level.Conclusions: Volume loading evokes biphasic changes in SNA through the resetting of CSP‐SNA relation in ABR. LBR is a powerful modulator of sympathetic nervous system.
Effects of treatment with pyridostigmine on ECG, hemodynamics and connexin 43 after acute myocardial infarct in anesthetized rats (1169.13)
Authors: Santos Fernanda , Silva Carlos Alberto , Fazan Rubens , Girao Henrique 
Published: June 2021

We evaluated the effect of acute treatment with pyridostigmine (PYR) an acetilconinesterase inhibitor on hemodynamics, ECG, survival rate and connexin 43 (Cx43), shortly after myocardial infarction (MI) in anesthetized rats.Rats were anesthetized with urethane, and instrumented for ECG and arterial pressure (AP) recordings. After basal recordings, acute MI was induced by left coronary artery ligation followed by treatment with PYR (0.25 mg/kg, iv), or saline. ECG and AP were monitored during for 4h after MI when the animals had their hearts removed and retrogradely perfused with a Evans blue dye to determine the size of myocardial ischemia. The amount of Cx43 in left ventricle was also evaluated, by Western blot technique, in left ventricle of infarcted rats.PYR caused a mild reduction in heart rate (438±8 to 387±10 bpm) with no change in AP. Infarcted rats treated with PYR showed lower incidence of arrhythmias and the percentage of rats that survived until the 4th hour after infarction was also higher in subjects that received PYR (72 vs 58%). Lengthening of QTc interval (Δ=33±13 ms) was observed in non‐treated, but not in PYR treated rats (Δ=‐2±4 ms). Finally, the amount of Cx43 in left ventricle was markedly reduced after MI (2.2±0.4 vs 0.72±0.1 au in non‐infarcted control rats). PYR administration also prevented the reduction in Cx43 (1.31±0.29 au) of infarcted rats.Grant Funding Source: Supported by FAPESP, CNPq, CAPES, FAEPA.
TrkA mediated translocation of TRPv1 receptor is reduced in afferent neurons of cadiomyopathic rats (1169.16)
Authors: Nguyen Minh , Stout Laurence , Li Qinglu , Garry Mary 
Published: June 2021

Previous studies have suggested that the decreased activity of TRPv1 receptor, a vanilloid receptor, plays a role in the development of an exaggerated exercise pressor reflex observed in the cardiomyopathic (CM) rat model. A requirement of TRPv1 activity is its localization to the cell membrane, which is mediated by the TrkA receptor. To determine if the translocation of TRPv1 is impaired in CM rats, we compared the levels of TRPv1 in the cell membranes of neurons from dorsal root ganglia (DRG) from normal and CM rats. Cells were stained for TRPv1 and fluorescence intensities of membrane and total cell were quantified. Localization of TRPv1 was evaluated in the presence or absence of Nerve Growth Factor (NGF) stimulation, and with a TrkA inhibitor in the presence of NGF. NGF treated neurons from normal animals displayed an increased ratio of membrane to total cell (M:T) TRPv1 as compared to untreated control. The addition of a TrkA inhibitor returned M:T to the level of non‐stimulated neurons. In the neurons from CM rats, NGF failed to increase the M:T, and treatment with TrkA inhibitor also did not change M:T level. These results suggest that DRG from CM rats are defective in their ability to translocate TRPv1 to the membrane upon NGF stimulation and this occurs via the TrkA receptor pathway.Grant Funding Source: Supported by NIH 2R01HL070242‐07A2 (MGG)
Blueberries exert antihypertensive and vascular‐protective effects in postmenopausal women with pre‐ and stage 1‐hypertension (117.6)
Authors: Johnson Sarah , Figueroa Arturo , Navaei Negin , Wong Alexei , Kalfon Roy , Feresin Rafaela , Elam Marcus , Payton Mark , Arjmandi Bahram 
Published: June 2021

Postmenopausal women have a high prevalence of hypertension (HTN) and often develop arterial stiffness which increases their risk for developing cardiovascular disease. Although antihypertensive drug therapies exist, increasing numbers of people prefer natural therapies. In vivo studies have demonstrated the antihypertensive and vascular‐protective effects of blueberries. Therefore, the objective of this study was to examine the effects of 22 g freeze‐dried blueberry powder (BB) or 22 g control (CON) per day for 8 weeks on blood pressure and arterial stiffness in forty postmenopausal women with pre‐ and stage 1‐HTN. Resting brachial systolic and diastolic blood pressures (SBP and DBP, respectively) were evaluated and arterial stiffness was assessed using carotid‐femoral pulse wave velocity (cfPWV) and brachial‐ankle pulse wave velocity (baPWV). Blood was collected at baseline, 4 and 8 weeks to assess nitric oxide (NO). After 8 weeks of BB treatment, SBP and DBP (– 7 mmHg, P < 0.05 and – 5 mmHg, P < 0.01, respectively) and baPWV (– 97 cm/s, P < 0.01) were significantly lower than baseline levels and there were significant (P < 0.05) group by time interactions, whereas there were no changes in CON. NO levels were significantly (6.24 µM, P < 0.01) increased in the BB group at 8 weeks compared to baseline values whereas there were no changes in CON. The results of this study indicate that regular consumption of blueberries is of benefit to vascular health.Grant Funding Source: Supported by The U.S. Highbush Blueberry Council
Daily almond consumption (1.5 oz./d) decreases abdominal and leg adiposity in mildly hypercholesterolemic individuals (117.8)
Authors: Berryman Claire , West Sheila , Fleming Jennifer , Bordi Peter , Kris‐Etherton Penny 
Published: June 2021

Almonds are an energy‐dense food that do not promote weight gain or increased waist circumference (WC); however, the effects of almond consumption on total body and sub‐regional fat and lean mass distribution have not been evaluated. Therefore, a randomized, 2‐period (6 wk/period), crossover, controlled‐feeding study was designed to investigate the effects of 1.5 oz./d almonds vs. a calorie‐matched, high CHO snack, within the context of a cholesterol‐lowering diet, on measures of body composition. Differences in nutrient profiles of the control (CON: 58% CHO, 15% PRO, 26% FAT, no almonds/d) and almond (ALD: 51% CHO, 16% PRO, 32% FAT, 1.5 oz. of almonds/d) diets were due to nutrients inherent to each snack and did not differ in saturated fat or cholesterol. Subjects (n=52) were generally healthy adults (BMI 26.3 ± 0.4 m/kg2) with elevated LDL‐C (148.0 ± 2.7 mg/dl). Total body mass (weight), fat mass, and lean mass were not different on the two diets. ALD reduced overall abdominal mass, abdominal fat mass, and abdominal lean mass vs. CON (‐0.20 ± 0.08, ‐0.07 ± 0.03, and ‐0.13 ± 0.06 kg, respectively; P 蠄0.04). WC also was decreased by ALD compared to CON (‐0.67 ± 0.31 cm; P=0.03). Moreover, ALD decreased leg fat mass compared to CON (‐0.12 ± 0.05; P=0.02). Incorporation of almonds in a cholesterol‐lowering diet decreases sub‐regional fat depots, including abdominal adiposity, an important risk factor for metabolic syndrome.Grant Funding Source: Supported by the Almond Board of California
Increased pressure gradient across veins in human limbs induces sympathetic activation (1170.1)
Authors: Cui Jian , Blaha Cheryl , Herr Michael , Muller Matthew , Drew Rachel , Sinoway Lawrence 
Published: June 2021

We showed that venous distension induced by saline infusion into veins of an arterially occluded arm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We have also observed that negative pressure on an occluded limb increases MSNA. We speculate that the responses with these two models are evoked through a similar mechanism. To examine this question, BP, heart rate, and MSNA were assessed in 11 young healthy subjects, when 100 mmHg negative pressure was applied on an arterially occluded limb (termed “NPOL”) for 2 min. Limb occlusion without suction was used as a control. In a separate visit, saline (5% arm volume) was infused into veins of the arterially occluded arm. Both NPOL and the saline infusion into the occluded arm significantly increased MSNA and BP. Both MSNA (R=0.643 for arm, R=0.664 for leg) and BP (R=0.786 for arm, R=0.522 for leg) responses during NPOL were significantly correlated with the responses with the saline infusion into the arm. The MSNA and BP responses during saline infusion were not correlated with the responses during limb occlusion. These observations suggest that the mechanisms responsible for sympathetic activation during limb suction are similar to those seen during infusion induced venous distension. Thus, the NPOL model can be employed to study the venous distension reflex.Grant Funding Source: Supported by NIH P01 HL096570 (LIS) and UL1 TR000127 (LIS)
Sensory nerve‐mediated vasodilation is reduced in plantar metatarsal arteries from spinal cord injured rats (1170.15)
Authors: Brock James , Shafik Christopher 
Published: June 2021

Axon‐reflex mediated vasodilation is reduced in skin of spinal cord injured humans (SCI). This change is suggested to produce altered skin function, an increased risk of pressure sores and slow wound healing. This study investigated the interaction between sympathetic and sensory nerve‐mediated effects in plantar metatarsal arteries (PMAs) from T10 spinal cord transected and sham‐operated (control) rats. Six weeks post‐surgery, PMAs were dissected and mounted isometrically in wire myographs. In control PMAs, activation of the perivascular nerve fibers with trains of 100 pulses at 1 Hz evoked contractions that peaked at ~10th pulse (1.1 ± 0.1 mN/mm) and then declined to ~40% (41 ± 5%) of the peak value at the 100th pulse. In PMAs from SCI rats, the peak amplitude of contraction was ~2‐fold larger (2.1 ± 0.2 mN/mm, P < 0.01) and the decline during the train of stimuli was smaller (declined to 94 ± 5 % of peak value). Treatment with capsaicin to inhibit the vasodilator action of the primary afferent nerve fibers did not greatly change the peak amplitude of nerve‐evoked contractions in PMAs from either control or SCI rats. However, in control PMAs, the decline in contraction during the train of stimuli was markedly reduced, with the contraction measured at the 100th pulse being increased by ~155% (155 ± 40 %). The % increase in amplitude of contractions measured at 100th pulse was much smaller in PMAs from SCI rats (20 ± 6%, P < 0.01). In conclusion, these findings indicate that the decline in sympathetic nerve‐mediated contraction during trains of stimuli is produced by co‐activation of primary afferent nerve fibers and that this effect was greatly reduced in PMAs from SCI rats. This finding may explain why axon reflex‐mediated vasodilation is reduced in skin of SCI humans.Grant Funding Source: Supported by the NHMRC of Australia
Exploring social stress though pharmacological manipulation of pair bonds in prairie voles (1171.2)
Authors: McNeal Neal , Scotti Melissa‐Ann , Woodbury Matthew , Ihm Elliott , Colburn William , Cacioppo Stephanie , Cacioppo John , Grippo Angela 
Published: June 2021

Supportive social relationships positively influence health, whereas negative relationships have an adverse effect. This preliminary experiment investigated the hypothesis that suppressing central oxytocin activity in male prairie voles would alter pair interactions, thereby inducing behavioral and cardiovascular changes in their associated female partners. Female prairie voles were implanted with radiotelemetry transmitters and paired with an unrelated male. In phase 1, male partners received 7 days of an oxytocin antagonist (OTA; 10mg/kg/day ip) concurrently during housing with the females. Depressive behaviors and cardiovascular function were measured in the females. Females whose male partners received OTA displayed higher resting blood pressure (BP) and heart rate (HR), and higher levels of depression‐like behaviors in a behavioral test, vs. those whose partners received vehicle. In phase 2, females were isolated from the male partners for 6 days, plus 6 days of additional mild stressors. Females exhibited higher BP and HR, regardless of whether the male partner previously had received OTA or vehicle. These preliminary findings indicate that oxytocinergic mechanisms may underlie male‐female social interactions to influence responses to stress, and inform our understanding of the role of social relationships in mediating stressor reactivity in humans.Grant Funding Source: HL112350
Reflex control of renal sympathetic nerve activity in heart failure is preserved in ovary intact female rats (1171.3)
Authors: Pinkham Maximilian , Guild Sarah‐Jane , Malpas Simon , Barrett Carolyn 
Published: June 2021

Following myocardial infarction (MI), pathological increases in sympathetic nerve activity (SNA) drive the development and progression of heart failure. The current study investigated the effects of female sex and ovarian hormones on arterial baroreflex and cardiac sympathetic afferent reflex (CSAR) control over renal SNA in MI‐induced heart failure. 6 weeks post MI or sham surgery , arterial pressure and renal SNA responses were recorded in chloralose‐urethane anesthetized male, female and ovariectomized female (OVX) rats. In male and OVX MI groups, arterial baroreflex control of renal SNA was significantly impaired compared to shams, due mostly to an impaired ability to inhibit SNA. In ovary‐intact females, arterial baroreflex control of renal SNA was unaltered in MI animals compared to sham. CSAR mediated increases in renal SNA were significantly augmented in male and OVX MI groups when compared to ovary‐intact female MI group. The current study is the first to describe a protective effect of ovarian hormones on reflex control of SNA in MI‐induced heart failure.Grant Funding Source: Lottery Health New Zealand and University of Auckland Faculty Research Development Fund
Pregnancy increases sympathetic nerve activity: role of the arcuate nucleus (1171.5)
Authors: Shi Zhigang , Brooks Virginia 
Published: June 2021

Normal pregnancy increases sympathetic nerve activity (SNA), which is further elevated in hypertensive disorders like preeclampsia. However, the mechanisms are unknown. The arcuate nucleus (ArcN), recently identified as a regulator of SNA, undergoes profound changes during pregnancy and other reproductive states. Therefore, we tested the hypothesis that the ArcN contributes to the elevated SNA during pregnancy, by determining if inhibition of the ArcN with the GABAA agonist, muscimol (30 pmol in 30 nL), decreases SNA and mean arterial pressure (MAP) more in late pregnant (P) compared to nonpregnant (NP) SD α‐chloralose anesthetized rats. Compared to NP rats, P rats exhibited lower MAP (P: 83±3 mmHg, n=12; NP: 111±4 mmHg, n=13; P<0.05), higher HR (P: 420±8 bpm, n=12; NP: 367±12 bpm, n=13; P<0.05), elevated lumbar SNA (LSNA; P: 1.9±0.2 µV, n=4; NP: 0.6±0.2 µV, n=4; P<0.05) and elevated splanchnic SNA (SSNA; P: 3.5±0.7 µV, n=4; NP: 0.9±0.2 µV, n=5; P<0.05); renal SNA (RSNA) was not significantly different between groups (P: 5.3±1.7, n=4; NP: 4.2±0.9 µV, n=4). In pregnant rats, ArcN nanoinjection of muscimol significantly decreased (P<0.05) MAP (‐13.3±1.6 mmHg), HR (‐14.5±1.6 bpm), LSNA (‐14.9±3.1% control), SSNA (‐14.4±1.8 % control), and RSNA (‐12.6±0.6 % control). ArcN muscimol did not significantly alter these variables in NP rats. In conclusion, these data suggest that, during pregnancy, the ArcN contributes to sustained increases in sympathetic tone to multiple organs.Grant Funding Source: Supported by HL088552 and AHA.
Tonic GABAergic inhibition of RVLM neurons: a novel target for sympathetic control (1172.3)
Authors: Gao Hong , Derbenev Andrei 
Published: June 2021

The rostral ventrolateral medulla (RVLM) is a critical component of the sympathetic nervous system regulating homeostatic functions including arterial blood pressure (ABP). GABAA receptors mediate the majority of inhibition in the brain and GABAergic inhibition of preautonomic neurons in the RVLM is well accepted. Decreased inhibition of RVLM neurons increases sympathetic nervous system activity and thereby elevates ABP. Despite our increasing understanding of the functional significance of GABAA receptors in the regulation of neuronal excitability, the mechanisms underlining synaptic and extrasynaptic control of preautonomic neurons in the RVLM is unknown. Using the transsynaptic retrograde viral tracer, PRV‐152, we identified preautonomic neurons in the RVLM. We found that RVLM neurons displayed persistent, tonic current to GABA, via GABAA receptors, in the absence of large‐scale phasic neurotransmission using whole‐cell patch‐clamp recordings. Application of the GABAA receptor blocker bicuculline (30 µM), revealed a robust somatic tonic inhibitory current mediated by extrasynaptic GABAA receptors with an average amplitude of 196.3 ± 39.3 pA. Our data suggest that extrasynaptic tonic current mediated by GABAA receptors plays a major role in determining the resting membrane potential and firing activity of preautonomic neurons in the RVLM.Grant Funding Source: NIH P30GM103337
Relaxation of human airway smooth muscle cells (1174.1)
Authors: Fitzgerald Robert , Lee Danielle , Panettieri Reynold , Wang Rui , An Steven 
Published: June 2021

The purpose of this study was to determine if H2S relaxed human airway smooth muscle cells. If so, we explored the mechanisms responsible for the phenomenon. Human airway smooth muscle cells (HASM) were prepared from human bronchi obtained from lungs unsuitable for transplantation. Dynamic changes in stiffness were measured as an indicator of contraction and relaxation of isolated HASM, using Magnetic Twisting Cytometry (MTC). Acute exposure of the cells to two agents capable of generating H2S, Na2S and GYY4137, decreased cell stiffness in a dose‐dependent fashion, with maximal relaxation at 10mM and 5mM, respectively. In addition, cells exposed to varying doses of GYY4137 for 24 hours exhibited dose‐dependent decreases in cell stiffness that were substantially greater than acute responses (21% relaxation at 300s vs 50% relaxation at 24h). We further determined that, like vascular smooth muscle, HASM exhibited the presence of ATP‐sensitive K channels and the H2S synthesizing enzyme, cystathionine‐g‐lyase. These findings demonstrated that smooth muscle in the airways react to H2S quite similarly to that in the vasculature, and suggest, thereby, this class of small gas molecules can be exploited for treating constricted human airways, such as found is asthma.Grant Funding Source: HL50712‐13 HL107361
Non‐genomic relaxation effect of testosterone through L‐type and store operated Ca2+ channels blockade in guinea pig airway smooth muscle (1174.2)
Authors: Montaño Luis , Perusquía Mercedes , Flores‐Soto Edgar 
Published: June 2021

In vascular smooth muscle, testosterone (TES) produces relaxation blocking L‐type Ca2+ channels. Recently, we found that L‐type and store operated (SOC) Ca2+ channels are the main membranal structures that provide extracellular Ca2+ for carbachol‐induced contraction in airway smooth muscle (ASM). Thus, we studied the possible interactions between L‐type and SOC channels in TES‐induced relaxation in guinea pig ASM. TES (10, 32 and 100 μM) induced a complete relaxation of Cch pre‐contracted tracheal smooth muscle and indomethacin partially inhibited this response. In single myocytes, the KCl induced intracellular Ca2+ increase ([Ca2+]i) was decreased by 32 and completely blocked by 100 nM TES. This androgen (32 and 100 μM) significantly diminished (~25 and 49 %, respectively) the capacitative Ca2+ entry. Myocytes stimulated with carbachol (Cch) produced a transient Ca2+ peak followed by a sustained plateau and 100 μM TES completely abolished the Cch induced Ca2+ plateau. Indomethacin, significantly diminished this effect of TES. When D‐600 was added during the plateau phase, a partial diminution (~35 %) was observed. A grater decrease (~78 %) was also seen when 2‐APB (SOC antagonist) was used. The combination of both drugs completely abolished the Ca2+ plateau induced by Cch. We concluded that TES blocks L‐type Ca2+ channels at nanomolar and SOC channels at micromolar concentration to induce relaxation.Grant Funding Source: PAPIIT‐DGAPA, UNAM IN200613
mAChR activation induces epithelial‐mesenchymal transition on lung epithelial cells (1176.10)
Authors: Li Juan , Xu Lu , Cui Yong‐Yao , Chen Hong‐Zhuan 
Published: June 2021

Objective: Epithelial‐mesenchymal transition (EMT) is a physiological process that plays important role in pathogenesis of chronic obstructive pulmonary disease (COPD). Although a number of molecules involved in ACh‐mediated airway inflammation and remodeling have been identified, little is known regarding the role of ACh in EMT. In this study, we examined the effects of ACh on TGF‐β1‐induced EMT, and the pathway involved in these processes Methods: Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated using western blot and immunofluorescence analyses.Results: Decreased E‐cadherin expression and increased vimentin and α‐SMA expression induced by TGF‐β1 in the human alveolar epithelial cell line (A549) were significantly abrogated by the non‐selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event in lung epithelial cells also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF‐β1 which release also trigged by ACh analogue carbachol. Interestingly, mAChR stimulation with carbachol also induced EMT in alveolar epithelial cells (A549) as well as in bronchial epithelial cells (16HBE) in a time‐ and concentration‐dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4‐DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Carbachol‐induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was also inhibited by pirenzepine and 4‐DAMP.Conclusions: Our findings indicate that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and a cooperative regulation by mAChR activation and TGF‐β1 expression was involved in EMT, leading to airway remodeling.Grant Funding Source: Supported by National Natural Science Foundation of China Nos.30873109 and 81173084