bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to environmentally relevant concentration of second hand smoke increased blood pressure and decreased baroreflex sensitivity in mice
Authors: Pan Shiyue , Karey Emma , Chen Yi‐Je , Nieves‐Cintron Madeline , Pinkerton Kent E , Chen Chao 
Published: June 2021

BACKGROUNDSecond hand smoke (SHS), a main indoor air pollution, is a significant risk factor for cardiovascular morbidity and mortality. Epidemiological studies link SHS exposure to increased sympathetic nerve activity (SNA) and blood pressure (BP), suggesting a central component in SHS‐induced cardiovascular dysregulation. However, we have limited information on effects of SHS on baroreflex sensitivity (BRS), an indicator of central regulation of BP and a stronger link to cardiovascular morbidity and mortality than the elevated BP. Additionally, we lack information on whether exposure to environmentally relevant levels of SHS affects BP regulation. Here we sought to test the hypothesis that chronic exposure to an environmentally relevant level of SHS elevates BP and reduces BRS.METHODSAdult male C57BL/6J mice (11 wk old) were implanted with BP/ECG telemetry devices. After two weeks of recovery from surgery, mice were randomly assigned to either filtered air (FA, n=18) or SHS (n=14) for up to 12 weeks. The SHS exposure level was similar to that of a smoky bar (3 mg/m3, 6 hr/d, 5 d/wk). 36 hours of continuous BP and ECG recordings were performed after the 5th day of exposure each week. Data were divided into three 12‐hr periods based on light cycle: dark 1, light and dark 2. Standard deviation of beat‐to‐beat BP was taken as the BP variability (BPV). BRS was determined with the sequence method using systolic BP.RESULTSThere was no difference in body weight between FA‐ and SHS‐exposed mice over the 12‐wk period. SHS exposure had no effect on dark‐light difference in BP, BPV, and BRS. Comparing to FA mice, SHS mice had higher systolic BP (~2.4 mmHg, p < 0.05), mean BP (~3 mmHg, p <0.05), and diastolic BP (~4 mmHg, p < 0.05) by 4 weeks of exposure. SHS reduced pulse pressure (PP, ~2 mmHg, p < 0.05), although the magnitude of the reduction diminished over time. In contrast, the SHS‐induced reduction in BRS was time dependent and accumulative, having a slower onset than changes in BP and PP, and becoming more severe with increasing exposure duration (−0.8%, −6.2%, and −12.3% for 4, 8, and 12 wk, respectively). SHS did not change BP variability, regardless of exposure duration.CONCLUSIONSThe effect of SHS on increased BP was observed after 4 wk of exposure and sustained through 12 wk of exposure. In contrast, SHS‐induced reductions in BRS showed a delayed onset that accumulates with prolonged exposures. The data suggest that SHS may activate multiple mechanisms resulting in BP dysregulation.Support or Funding InformationR01 ES025229This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Sex on Cardiovascular Responses to Acute Sympathoexcitatory Stressors
Authors: Coovadia Yasmine , Adler Tessa Evangeline , Usselman Charlotte Willemina 
Published: June 2021

Over the past twenty years, an increasing number of studies have compared baseline cardiovascular regulation between men and women. These studies have provided strong support for an effect of sex on cardiovascular outcomes, and implicate the sympathetic nervous system as a mediator of many of these differences. However, many of these studies have been conducted under baseline conditions, despite the fact that humans are seldom in a true “baseline” state (i.e., quiet, supine rest). Therefore, the purpose of this study was to investigate the effect of sex on cardiovascular responses to sympatho‐excitatory stimuli in young healthy individuals. We examined cardiovascular responses to the cold pressor test (CPT) and a voluntary end‐expiratory apnea (APN) in 5 women and 4 men. We hypothesized that women would demonstrate a reduced change in total peripheral resistance (TPR) and therefore blood pressure (BP) responses to these stimuli compared with men. Men and women were of similar age (men: 24 ± 2 y, women: 24 ± 1; p=0.8) and BMI (men: 26 ± 6 kg/m2, women: 22 ± 1; p=0.2). Baseline mean arterial pressure (MAP) was higher in men than women (87 ± 7 vs77 ± 4 mmHg, respectively; p=0.03), while baseline TPR (men: 25.7 ± 2.7 vs women: 23.2 ± 6.6 mmHg/L/min; p=0.5) and cardiac output (3.4 ± 0.4 vs 3.5 ± 0.9 L/min; p=0.9) were similar between the sexes. CPT was associated with a significant increase in MAP from baseline which was not different between the sexes (men: 90 ± 3 vs women: 92 ± 13mmHg; main effect of condition: p=0.03, effect of sex: p=0.7). Likewise, TPR increased in response to CPT, but again this response did not differ between the sexes (men: 27.0 ± 7.1, vs women: 25.8 ± 5.4 mmHg/L/min; main effect of condition: p=0.04, effect of sex: p=0.3). APN‐EX was associated with a similar increase in DBP (men: 83 ± 6 vs women: 69 ± 25 mmHg; main effect of condition: p=0.03, effect of sex: p=0.3) as well as TPR (men: 33.0 ± 4.8 vs women: 29.0 ± 13.9 mmHg/L/min; main effect of condition: p=0.01, effect of sex: p=0.6). In conclusion, cardiovascular responses to the CPT, a generalized sympathetic stressor, as well as to APN, which activates the chemoreflex, were similar between the young healthy men and women. These data refute our hypothesis, and suggest that cardiovascular responsiveness during these sympatho‐excitatory stimuli does not differ between the sexes.Support or Funding InformationThis project was supported by a Natural Sciences and Engineering Research Council Discovery Grant (CWU). TEA and YC were supported by the McGill Department of Kinesiology and Physical Education Graduate Excellence Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle Sympathetic Nerve Activity Responses to Hypercapnia in Exercise Trained and Sedentary Adults
Authors: Eisenmann Nicole A , Howery Anna J , Harvey Ronee E , Barnes Jill N 
Published: June 2021

Elevated activity of the sympathetic nervous system at rest and sympathetic hyperreactivity to stress have been shown to be predictors for the development of cardiovascular diseases, such as hypertension. Previous studies have shown that there is no difference in resting muscle sympathetic nerve activity (MSNA) with exercise in young adults; however, the effects of exercise on the sympathoexcitatory response to chemical stimuli, such as hypercapnia, have not been studied. The purpose of this study was to compare MSNA responses to hypercapnia in young exercise trained and sedentary adults. Twenty‐nine young healthy adults were evaluated including 16 exercise trained (EX: M/F = 7/9; age = 27 ± 5 years; BMI = 23 ± 2 kg/m2) and 13 sedentary controls (CON: M/F = 7/6; age = 28 ± 4 years; BMI = 25 ± 2 kg/m2). Mean arterial pressure (MAP), heart rate (HR) and MSNA were measured continuously throughout the protocol. After baseline measurements were recorded, participants underwent a stepped hypercapnic protocol increasing to 6% CO2. Results are reported as mean ± SE. MAP was not different between groups at baseline (EX: 95 ± 4 mmHg vs. CON: 91 ± 5 mmHg; p>0.05) and during 6% CO2 (EX: 96 ± 4 mmHg vs. CON: 101 ± 5 mmHg; p>0.05). Both the change in MAP (EX: 1 ± 4 mmHg vs. CON: 11 ± 5 mmHg; p<0.05) and % change in MAP (EX: 2 ± 4 % vs. CON: 13 ± 5 %; p<0.05) were greater in the CON group compared with the EX group. HR was greater in the CON group compared with the EX group at baseline (EX: 50 ± 1 bpm vs. CON: 59 ± 3 mmHg; p<0.05) and during 6% CO2 (EX: 57 ± 2 bpm vs. CON: 68 ± 3 bpm; p<0.05). Both the change in HR (EX: 8 ± 1 bpm vs. CON: 9 ± 2 mmHg; p>0.05) and % change in HR (EX: 16 ± 3 % vs. CON: 16 ± 4 %; p>0.05) were not different between groups. MSNA was not different at baseline (EX: 16 ± 1 bursts/min vs. CON: 18 ± 2 bursts/min; p>0.05) and during 6% CO2 (EX: 17 ± 2 bursts/min vs. CON: 20 ± 2 bursts/min; p>0.05). The change in MSNA was greater in the CON group compared with the EX group (EX: 0.5 ± 0.4 bursts/min vs. CON: 2.4 ± 0.9 bursts/min; p<0.05) and the percent change in MSNA was non‐significant but tended to be higher in the CON group compared with the EX group (EX: 4 ± 2 % vs. CON: 16 ± 6 %; p=0.057). The sympathetic response to hypercapnia was lower in young exercise‐trained adults compared with sedentary adults. Taken together, these results suggest that hypercapnia‐induced sympathoexcitation may be altered with exercise training status, even in young healthy adults.Support or Funding InformationNIH HL118154This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Global REACH Expedition: Chronic Hypoxia Attenuates the Contribution α‐Adrenergic Receptors to Sympathetic Transduction in Exercising Humans
Authors: Hearon Christopher M , Hansen Alex B , Moralez Gilbert , Romero Steven A , Levine Benjamin D , Lawley Justin S 
Published: June 2021

IntroductionAcute exposure to hypoxia causes a rise in sympathetic nervous system activity (SNA) that restrains peripheral vasodilation. In normoxia, α‐adrenergic receptors are the primary mechanism eliciting vasoconstriction in response to increased SNA at rest and during exercise. However, exposure to chronic hypoxia (CH) causes a sustained and marked increase in SNA that is offset by reduced neurovascular transduction (vasoconstriction). Data from animal models indicate that CH blunts α‐adrenergic vasoconstrictor signaling, termed ‘hypoxic sympatholysis’. In humans it is unknown how CH alters α‐adrenergic restraint of skeletal muscle vascular tone at rest and during exercise.PurposeTo test the hypothesis that CH reduces α‐adrenergic restraint of forearm skeletal muscle vascular tone at rest and during sympathoexcitation in response to cycle exercise.MethodIn 9 healthy lowland natives, we measured forearm blood flow (Doppler ultrasound), mean arterial pressure (MAP, intra‐arterial catheter), heart rate (HR, ECG) and calculated changes in vascular conductance (ΔFVC) during semi‐recumbent cycle exercise (60% VO2 max) at baseline (BL: 344m) and after three weeks sojourn at high‐altitude (CH: 4,380m). Sympathetic α‐adrenergic restraint of vascular tone was assessed via intra‐arterial infusion of phentolamine (PHT, α‐adrenergic antagonist) to achieve local forearm α‐adrenoceptor blockade. All data are quantified as mean ± SD.ResultsAt rest, FVC was not lower in CH (BL: 38.0 ± 9.3 vs. CH: 32.6 ± 15.1 ml/100 mmHg/min; p=0.17). Local α‐adrenergic blockade increased FVC at BL and in CH (ΔFVC during PHT: BL: 70.0 ± 35.5 vs. CH: 87.7 ± 69.2 ml/100mmHg/min; P=0.59), indicative of significant residual basal α‐adrenergic restraint of vascular tone in CH. In contrast, the forearm vasoconstrictor response to 60% cycle exercise was attenuated by ~50% in CH (%ΔFVC during exercise: BL: −42.7 ± 29.6 vs. CH: −21.6 ± 19.4; P<0.05). Local α‐adrenergic blockade attenuated the vasoconstrictor response to exercise by 80% at BL (%ΔFVC during exercise: BL: −38.7 ± 34.2 vs. PHT: −6.1 ± 26.3; P<0.05). However, local α‐adrenergic blockade had no impact on the vasoconstrictor response to exercise in CH (%ΔFVC during exercise: CH: −21.6 ± 19.4 vs. PHT: −18.9 ± 12.1; P=0.77).ConclusionExposure to CH did not significantly alter basal α‐adrenergic restraint of forearm skeletal muscle vascular tone. However, CH attenuates the forearm vasoconstrictor response to cycle exercise, and the contribution of α‐adrenergic receptor‐mediated vasoconstriction is abolished, indicating a reliance on alternative vasoconstrictor mechanisms.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Response of Neurons in the Rostral Ventrolateral Medulla (RVLM) to Anticipated and Passive Movements
Authors: Bielanin John P , Miller Derek M , Joshi Asmita , Engstrom Isaiah C , Kambouroglos Emmanuel , McCall Andrew A , Barman Susan M , Yates Bill J 
Published: June 2021

It is well‐established that the rostral ventrolateral medulla (RVLM) plays a predominant role in regulating the activity of sympathetic outflow to the cardiovascular system. We and others have previously shown that in addition to baroreceptor inputs, RVLM neurons respond to signals from the vestibular system. However, most recordings of RVLM unit activity have occurred in anesthetized or decerebrate preparations, limiting the assessment of cognitive effects on neuronal activity. In this study, felines were instrumented for chronic recordings of the electrocardiogram and/or carotid artery blood flow as well as activity of RVLM neurons during 40° head‐up tilts. RVLM units were identified through stereotaxic coordinates and having activity correlated with changes in blood pressure during the cardiac cycle. Tilts were preceded by a light cue, so animals anticipated the movement. We tested the hypothesis that head‐up tilts elicit an increase in the activity of RVLM neurons that is initiated between the light cue and the onset of movement. We also determined if there is a relationship between RVLM unit activity and heart rate, as would be expected if the changes in firing rate are dictated by baroreceptor signals. Head‐up tilts elicited an increase in firing rate for a third of RVLM units. However, for the majority of these units, there was not a significant change in firing rate following the light cue and prior to head‐up rotations. In addition, linear regression analyses showed that there was no appreciable relationship between unit firing rate and heart rate (R2 values ranged from 0.001–0.29, median of 0.03). These studies suggest that cognitive inputs do not produce feedforward alterations in excitability of RVLM neurons prior to perturbations that can alter blood pressure. In addition, they show that inputs to RVLM neurons are complex such that the firing rate of the units is not simply related to baroreceptor inputs.Support or Funding InformationNIH grant R01‐DC013788This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Elevated muscle sympathetic nerve activity is independently associated with common carotid artery wall thickness in humans
Authors: Holwerda Seth W. , Luehrs Rachel E. , Pierce Gary L. 
Published: June 2021

Aging is characterized by increased wall thickness and stiffening of the large elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are incompletely understood. Studies in vitro demonstrate hypertrophy of vascular smooth muscle following chronic sympathetic‐adrenergic stimulation. In addition, higher measures of sympathetic nerve activity, which typically occur with advancing age, are associated with greater intima‐media thickness (IMT) of the large peripheral arteries such as the common femoral arteries. Therefore, we tested the hypothesis that the age‐related increase in large elastic artery (carotid) IMT would be independently associated with higher sympathetic nerve activity. In a cohort of 88 young and middle‐age/older adults (age: 19–73 yr, 52% men) with no history of cardiovascular disease, we performed assessments of muscle sympathetic nerve activity (MSNA, microneurography), common carotid IMT (ultrasonography), and ambulatory 24‐hr mean arterial pressure (MAP). As expected, advancing age was significantly correlated with higher MSNA burst frequency (R=0.54, P<0.001), carotid IMT (R=0.51, P<0.001), and ambulatory 24‐hr MAP (R=0.18, P=0.047). Results from multiple regression analysis that included MSNA burst frequency and traditional cardiovascular disease (CVD) risk factors that were also significantly correlated with carotid IMT (age, BMI, history of hypertension or borderline hypertension, family history of hypertension, and ambulatory 24‐hour MAP) showed that MSNA burst frequency (P=0.031), age (P=0.003), and ambulatory 24‐hour MAP (P=0.003) were independent determinants of carotid IMT (model R2=0.47, P<0.001). When expressing carotid IMT relative to lumen diameter (carotid IMT‐to‐lumen diameter ratio), multiple regression analysis showed that only MSNA burst frequency (P=0.02) was an independent determinant (model R2=0.36, P<0.001). These findings demonstrate an independent association between MSNA and carotid IMT and suggest that the age‐related increase in sympathetic‐adrenergic tone may contribute importantly to increased wall thickness of the large elastic arteries.Support or Funding InformationAHA (17POST33440101), T32 HL07121, NHLBI (P01HL014388), U54 TR001356 and AHA (13DG143400012).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathetic Transduction in Young Women with a Family History of Hypertension
Authors: McGinty Shane J. , Babcock Matthew C. , Matthews Evan L. , Greaney Jody L. , Wenner Megan M. 
Published: June 2021

Exaggerated sympathetic transduction has recently been demonstrated in certain populations of young adults at risk for future hypertension. Our laboratory has previously reported that young women with a family history of hypertension (+FH), a population with a greater risk for future hypertension, have exaggerated sympathetic and blood pressure (BP) reactivity compared to women without a family history of hypertension (−FH). However, it is unclear whether resting sympathetic transduction may partially explain the exaggerated BP reactivity in +FH women.PURPOSETherefore, the purpose of this study was to test the hypothesis that +FH young women would display augmented pressor responses following spontaneous bursts of muscle sympathetic nerve activity (MSNA) at rest.METHODSWe retrospectively examined beat‐by‐beat BP (finger photoplethysmography) and MSNA (peroneal microneurography) in 5 +FH (22 ± 1 yr, 20 ± 2 kg/m2) and 7 −FH young women (24 ± 3 yr, 21 ± 1 kg/m2) during 10 minutes of supine rest. Signal averaging was used to characterize changes in BP for the 10 cardiac cycles following spontaneous MSNA bursts. Resting baseline variables were compared using unpaired t‐tests. A 2‐way repeated measures ANOVA was used to compared BP changes over 10 cardiac cycles following a burst of MSNA, and peak BP changes were compared using unpaired t‐tests. Data are presented as mean ± SD.RESULTSResting mean arterial pressure (MAP) (+FH: 76 ± 12 vs. −FH: 83 ± 19 mmHg, p=0.72), MSNA (+FH: 8 ± 2 vs. −FH: 8 ± 5 bursts/min, p=0.89), heart rate (+FH: 70 ± 13 vs. −FH: 61 ± 4 bpm, p=0.12), and total peripheral resistance (+FH: 1811 ± 683 vs. −FH: 1432 ± 293 mmHg·min/mL, p=0.77) were not different between groups. Following spontaneous bursts of MSNA, the increase in MAP over the subsequent 10 cardiac cycles was not different between groups (time: p<0.01, group: p=0.16, interaction: p=0.89). Additionally, the peak change in MAP (+FH: Δ 1.5 ± 0.9 vs. −FH: Δ 2.4 ± 1.8 mmHg, p=0.35) systolic BP (+FH: Δ 1.6 ± 1.2 vs. −FH: Δ 3.7 ± 2.2 mmHg, p=0.18) and diastolic BP (+FH: Δ 2.2 ± 0.9 vs. −FH: Δ 3.5 ± 2.9 mmHg, p=0.73) were not different between groups.CONCLUSIONSThese preliminary data suggest that sympathetic transduction following a burst of MSNA at rest does not elicit greater increases in BP in +FH young women. Further research is needed in order to more specifically examine whether the degree to which a sympathetic burst influences vascular tone is altered in +FH women.Support or Funding InformationSupported by NIH Grant P20 GM 113125, P20 GM 103446, U54 GM 104941, and The University of Delaware Research FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardio‐Renal Syndrome Type 2: The Role of the Cardiac Spinal Afferent Reflex
Authors: Xia Zhiqiu , Han Li , Schiller Alicia , Pellegrino Peter R. , Lisco Steven J. , Zucker Irving H. , Wang Han‐Jun 
Published: June 2021

BackgroundCardio‐renal syndrome type II (CRS II) is defined as a chronic abnormality in cardiac function (chronic heart failure, CHF) causing progressive and potentially permanent chronic kidney disease. We hypothesized that the cardiac sympathetic afferent reflex (CSAR, a cardiogenic sympatho‐excitatory reflex mediated by spinal afferents from the heart) plays a critical role in the pathological development of CRS II. Specifically, we proposed that the CSAR control of sympathetic outflow to the kidneys exacerbates renal hypoperfusion and accelerates renal dysfunction including renal tubular damage in CRS II.MethodsWe examined the effects of acute or chronic activation/inhibition of the CSAR on renal blood flow (RBF), renal vascular resistance (RVR) and renal function in sham‐operated and myocardial infarction (MI) rats. Renal function was evaluated by measuring 1) blood creatinine and blood urea nitrogen (BUN) by iSTAT analysis; 2) urinary kidney damage markers such as the kidney injury molecule [KIM]‐1 and 3) RNA sequencing analysis (RNA‐Seq) in renal tissues.ResultsAcute CSAR activation by epicardial application of bradykinin (BK) in anesthetized, vagotomized rats resulted in an augmented increases in blood pressure, heart rate, and renal sympathetic nerve activity in MI compared to sham rats. CSAR activation also increased renal vascular resistance (RVR) to a greater extent in MI rats compared to sham rats. Chronic CSAR ablation by epicardial application of the highly specific TRPV1 receptor agonist resiniferatoxin (RTX) restored, in part, the decreased RBF and increased RVR in MI rats. Furthermore, epicardial RTX prevented the development of renal dysfunction at 4–5 months post MI as evidenced by decreased blood creatinine and BUN in MI+RTX rats. RNA‐Seq analysis showed that several renal injury and inflammatory gene markers were significantly upregulated by 30–100 fold at 18‐weeks post‐MI. Of those, the gene expression of KIM‐1 (a specific proximal tubular damage marker) was increased by ~70 fold in whole‐kidney tissue of MI rats compared to sham rats, whereas it was only increased by ~4 fold in rats treated with RTX. Compared to sham rats, MI rats exhibited much higher concentration of urinary Kim‐1 18 weeks post MI, which was largely prevented by RTX treatment.ConclusionThese data suggest that CSAR ablation by RTX may impart a selective protective effect on renal proximal tubular damage in CHF. Considering the fact that renal proximal tubules are located in the renal cortex where the majority of renal blood flow is distributed, it is very likely that chronic CSAR ablation improves renal proximal tubular damage by partially restoring cortical blood flow in CHF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.