bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Baroreflex‐Mediated Cardiovascular Responses to Acute Hypotension in Heart Failure Patients Compared to Healthy Adults
Authors: Drew Rachel C , Lindblad Chelsea N , Samii Soraya M , Blaha Cheryl A , White Michael J , Sinoway Lawrence I 
Published: November 2023

Patients with heart failure (HF) exhibit baroreflex dysfunction, which is associated with increased morbidity and mortality (Mortara et al., 1997). This baroreflex dysfunction, caused in part by heightened sympathetic activation and blunted parasympathetic activation (Floras and Ponikowski, 2015), results in inadequate reflex control of blood pressure (BP; Creager and Creager, 1994). Orthostatic hypotension, a decrease in BP upon standing, is a condition that often occurs in HF, and may be linked with altered baroreflex responsiveness in this population (Cody et al., 1982). However, data on baroreflex‐mediated cardiovascular responses to acute hypotension in HF patients are limited. Therefore, 8 HF patients (7 men; mean ± SEM 65 ± 3 y; 1.74 ± 0.04 m; 89 ± 5 kg; ejection fraction 30.5 ± 3.1 %) and 7 healthy control (CON) adults (6 men; 65 ± 2 y; 1.78 ± 0.03 m; 86 ± 6 kg) underwent 7.5 minutes of unilateral lower‐limb ischemia via inflation of a thigh cuff on one leg to non‐pharmacologically induce acute hypotension upon cuff deflation. Beat‐to‐beat systolic BP, diastolic BP, and mean arterial BP (MAP; photoplethysmographic finger cuff) and heart rate (HR; electrocardiogram) were recorded continuously before, during, and after cuff inflation. Statistical analysis involved independent‐samples t‐tests. Baseline values were not different between groups (systolic BP: 128 ± 8 vs. 128 ± 4 mmHg; diastolic BP: 73 ± 3 vs. 82 ± 5 mmHg; MAP: 90 ± 3 vs. 97 ± 4 mmHg; HR: 62 ± 2 vs. 56 ± 2 b.min−1 for HF and CON, respectively; P > 0.05). The magnitude of the induced decrease in MAP was similar in both groups (HF −11 ± 1 vs. CON −12 ± 2 mmHg; P > 0.05). However, the time‐to‐peak MAP decrease was significantly longer in HF compared to CON (HF 11 ± 2 vs. CON 6 ± 1 s; P < 0.05). The magnitude of the resultant HR increase was not different between groups (HF 2 ± 1 vs. CON 4 ± 1 mmHg; P > 0.05). However, the time‐to‐peak HR increase was longer in HF compared to CON (HF 9 ± 1 vs. CON 6 ± 1 s; P < 0.05). In conclusion, these results demonstrate that in response to acute hypotension, HF patients exhibit prolonged hypotension and a delayed tachycardic response. These findings suggest that baroreflex‐mediated cardiovascular responses to acute hypotension are altered in HF compared to CON, which may be linked to the higher occurrence of orthostatic hypotension experienced in this population.Support or Funding InformationSupported by National Institutes of Health grants UL1 TR000127 and P01 HL096570, and British Heart Foundation travel grant FS/12/18/29522
Device‐Guided Slow Breathing Lowers Blood Pressure and Muscle Sympathetic Nerve Activity Acutely in Prehypertensive Patients with Post‐Traumatic Stress Disorder (PTSD)
Authors: Park Jeanie , Downey Ryan , Kankam Melanie , Norrholm Seth , Rothbaum Barbara 
Published: November 2023

Patients with post‐traumatic stress disorder (PTSD) have elevated sympathetic nervous system (SNS) reactivity and impaired arterial and cardiovagal baroreflex sensitivity (BRS) that contribute to increased risk of developing hypertension and cardiovascular disease. Device‐ guided slow breathing (DGB) during which respiratory rate is guided to subphysiologic rates of ~5 breaths/min using a biofeedback device has been shown to lower blood pressure (BP) and sympathetic activity in hypertensive patients. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves arterial and cardiovagal BRS in Veterans with PTSD. In 10 prehypertensive Veterans with PTSD, we measured continuous beat‐to‐beat arterial BP, EKG, and muscle sympathetic nerve activity (MSNA) at rest, and during 15 minutes of DGB (RESPeRATE). BRS was assessed using the modified oxford technique by which BP was decreased and increased using intravenous boluses of nitroprusside and phenylephrine. Cardiovagal BRS and sympathetic BRS were quantified as the slope of the linear regression between systolic BP (SBP) and R‐R interval, and diastolic BP (DBP) and MSNA burst incidence (BI) and total activity (TA), respectively. BRS assessments were made once at baseline, and repeated once during the last 5 minutes of DGB. Study participants had prehypertension (mean BP 130±4/76±2 mmHg) and had confirmed PTSD. After 10 minutes of DGB, there was a significant reduction in SBP (by −9±2 mmHg, p=0.002) and mean arterial pressure (MAP, by −4±1 mmHg, p=0.009), and a trend towards reduced DBP (−2±1 mmHg, p=0.08). There was no significant change in HR (p=0.21) with DGB. There was also a significant reduction in MSNA burst frequency (29±3 vs. 21±2 bursts/min, p=0.009), and MSNA BI (46±4 vs. 35±4 bursts/100 heart beats, p=0.004) from baseline to end of DGB. There was no significant change in sympathetic BRS quantified using both MSNA BI (p=0.19) and total activity (p=0.22), or cardiovagal BRS (p=0.24), from baseline to during DGB. DGB acutely lowers BP and MSNA, but does not improve sympathetic or cardiovagal BRS in prehypertensive veterans with PTSD. Whether long‐term DGB chronically improves resting BP, SNS activity, and arterial BRS in PTSD should be tested in future studies.Support or Funding InformationSupported by VA Merit Grant 1I01CX001065; American Heart Association 15CSA24340001
Group III/IV muscle afferents contribute to carotid baroreflex resetting during evoked contractions in humans
Authors: Hureau Thomas J , Weavil Joshua C , Thurston Taylor S , Broxterman Ryan M , Nelson Ashley D , Bledsoe Amber D , Jessop Jacob E , Richardson Russell S , Wray D Walter , Amann Markus 
Published: November 2023

BackgroundArterial baroreflexes play an important role in the control and regulation of the cardiovascular response to exercise. In fact, carotid baroreflex control of arterial blood pressure needs to be reset during exercise to tolerate the higher blood pressures associated with physical activities. This resetting of carotid baroreflex control to operate at a higher blood pressure during exercise is thought to be mediated by both feedback and feed forward mechanisms.PurposeTo investigate the contribution of group III/IV muscle afferents to the carotid baroreflex control during evoked quadriceps contractions, devoid of feed forward input (i.e. no central command).MethodsEight recreationally active males (29 ± 5 yrs) performed electrically evoked isometric quadriceps contractions for 10 min (femoral nerve stimulation, 40 Hz, 50‐s on, 10‐s off) under control conditions (CTRL) and following lumbar intrathecal fentanyl (FENT) injection to impair feedback from μ‐opioid receptor sensitive lower limb muscle afferents. Carotid baroreflex function was assessed by applying rapid 5‐s pulses of neck pressure (NP, +40 mmHg) or suction (NS, −60 mmHg) via a customized collar. Heart rate (HR) and mean arterial pressure (MAP) were derived from a 12‐lead ECG and a radial arterial catheter, respectively. The carotid baroreflex operating point was determined using the average pre‐stimulus values for HR and MAP.ResultsResting HR (~70 bpm) and MAP (~87 mmHg) were similar between CTRL and FENT conditions (P > 0.4). FENT administration did not alter the cardiac response to NP (+9 ± 3 bpm; P = 0.99) or NS (−24 ± 11 bpm; P = 0.49) at rest. Similarly, FENT did not alter changes in MAP in response to NP (+13 ± 5 mmHg; P = 0.85) or NS (−13 ± 5 mmHg; P = 0.99) at rest. During exercise, FENT attenuated both HR (82 ± 10 bpm vs 93 ± 14 bpm; P < 0.05) and MAP (100 ± 14 mmHg vs 112 ± 14 mmHg; P < 0.05). However, similar to resting responses (P > 0.4), the cardiac response to NP (+11 ± 4 bpm) or NS (−23 ± 9 bpm) was similar during CTRL and FENT exercise (P > 0.5). Furthermore, changes in MAP in response to NP (+12 ± 4 mmHg) or NS (−14 ± 5 mmHg) were similar during CTRL and FENT exercise (P > 0.4).ConclusionInhibition of group III/IV muscle afferents during evoked muscle contractions reduced the operating point for both HR and MAP, suggesting this feedback pathway is important for carotid baroreflex resetting during exercise. However, carotid baroreflex responsiveness at rest and during exercise was preserved despite muscle afferent blockade, indicating that group III/IV muscle afferents do not govern the carotid baroreflex control of HR and MAP.Support or Funding InformationThe authors were supported by National Heart, Lung, and Blood Institute grants (HL‐103786 and HL‐116579) and a Veterans Affairs Spire grant (E1572P).
Effects of nitrous oxide sedation on sympathetic baroreflex sensitivity
Authors: Isono Kazushige , Okada Yoshiyuki , Mitsui Tatsuhisa , Higuchi Yudai , Masuda Yuji , Ogasawara Tadashi 
Published: November 2023

The number of patients with cardiovascular diseases is still growing worldwide, which may increase the risk for cardiovascular events associated with pain stimulation during medical and dental treatments. Nitrous oxide provides minimal and moderate sedation and suppresses pressor responses to pain. We found that an increase in heart rate (HR) in response to pain stimulation remained unchanged by nitrous oxide inhalation, while an increase in muscle sympathetic nerve activity (MSNA) was attenuated, suggesting that blood pressure (BP) control during nitrous oxide sedation may be modified via MSNA. We evaluated whether sympathetic baroreflex sensitivity (BRS) would be decreased by nitrous oxide sedation. Arm cuff and beat‐to‐beat BP (finger photoplethysmography), HR, MSNA (microneurography), cardiac output (Qc) and stroke volume (SV) were measured during inhalation of room air, 100% oxygen, 30%, 40% nitrous oxide, and room air (recovery) for 20 min through a mask, respectively, in 9 young men [age 31±2 (SD) yrs]. Sympathetic BRS was analyzed from the spontaneous changes in beat‐by‐beat diastolic BP and corresponding MSNA (burst incidence and total MSNA) during the last 5 min of each condition. Systolic and diastolic BP did not differ among the inhalation conditions. HR, Qc, and SV were also similar between any conditions. Sympathetic BRS was remained unchanged by inhalation sedation with any nitrous oxide concentration (burst incidence : −3.16 ±1.77, −2.98 ± .02, −2.86 ± 2.05, −2.19 ± 1.95, and−2.21 ± 1.34; P= 0.204 total MSNA : −6.56 ± 2.89, −6.79 ± 4.89, −6.89 ± 5.25, −4.75 ± 3.86, and −5.14 ± 3.44; P= 0.161). These results suggest that baroreflex function is maintained during nitrous oxide sedation and nitrous oxide itself does not directly affect BP regulations.Support or Funding InformationSupported by JSPSKAKENHI 16K20705.
Role of Brain Derived Neurotrophic Factor in the Supraoptic Nucleus on Response to Salt Loading
Authors: Balapattabi Kirthikaa , Little Joel T. , Bachelor Martha , Cunningham J. Thomas 
Published: November 2023

Previous studies have shown that Brain Derived Neurotrophic Factor (BDNF) contributes to ionic plasticity of vasopressin neurons from the supraoptic nucleus of the hypothalamus (SON) in response to 7 days of salt loading. This ionic plasticity is mediated by BDNF dependent phosphorylation of TrkB receptors and downregulation of KCC2, which alter chloride homeostasis resulting in impairment of baroreceptor inhibition of vasopressin release and an increase in mean arterial pressure that is partially vasopressin dependent. However, the specific source of BDNF is yet to be elucidated. In this study, we used adeno‐associated viral vectors with shRNA to test the hypothesis that the salt loading produces BDNF release from the SON which in turn contributes to changes in chloride homeostasis and increased blood pressure. Adult male Sprague Dawley rats (250–300 g b w) were anesthetized with isoflurane and bilaterally injected in the SON (300 nl) with either an AAV vector containing shRNA against BDNF or a control construct with an mCherry reporter. The vectors were injected at a titer of 1.0 × 1013 GC/ml (Vector Biolabs, Malvern, PA). Two weeks after the stereotaxic injections, some rats from each group were instrumented with radio telemetry transmitters using isoflurane anesthesia for recording mean arterial pressure and heart rate. Rats were then housed in commercial metabolism cages and given water or 2% NaCl to drink for 7 days. Volume of fluid intake, urine excretion, food intake, and body weight were measured during the study along with radio telemetry recording for heart rate, mean arterial pressure and activity. Brain regions were harvested for measuring gene expression and protein content at the end of the 7 days. Seven days of 2% salt loading increased TrKB phosphorylation in the SON of rats injected with the control vector. Virally mediated BDNF knockdown in the SON of salt loaded rats decreased TrkB phosphorylation. However, the increases in blood pressure produced by salt loading were not different between these two groups. Both salt loaded groups also had comparable decreases in body weight and increases in fluid intake. The results suggest that, while locally produced BDNF contributes to TrKB phosphorylation in the SON during salt loading, it is not necessary for the increase in blood pressure.Support or Funding InformationSupported by grant # R01 HL119458
The Temporal Effects of DOCA‐Salt on the Renal T Cell Profile is Sex‐Specific
Authors: Hutchinson Justin , Gillis Ellen E , Crislip G Ryan , Musall Jacqueline B , Baban Babak , Sullivan Jennifer C 
Published: November 2023

There is growing evidence for a role for T cells in the pathogenesis of hypertension. Previous studies by our laboratory show that hypertensive males have more pro‐inflammatory Th17 cells while females have more anti‐inflammatory T regulatory cells (Tregs); we propose that greater Tregs in females contribute to their lower blood pressure (BP) compared to males. The goal of the current study was to test the hypothesis that Tregs preferentially increase over time in female rats with increases in BP, while Th17 cells will increase to a greater extent in males. Male (M) and female (F) uni‐nephrectomized Sprague Dawley rats (10 weeks of age) were subcutaneously implanted with a deoxycorticosterone acetate (DOCA) pellet (200 mg/rat, 60‐day time release) and given 0.9% NaCl to drink. Subsets of rats were killed following 1, 2, and 3 weeks (wks) of DOCA treatment and kidneys were processed for flow cytometric analysis of T cells; n=6/group per time point. BP was measured in separate DOCA rats via telemetry (n=5–6). DOCA increased BP in both M (basal: 115±4, wk1: 146±3, wk2: 187±2, wk3: 190±2 mmHg; p<0.01) and F rats (basal: 105±3, wk1: 134±5, wk2: 165±8, wk3: 175±8 mmHg; p<0.01). BP was comparable between the sexes at baseline (p=0.2), wk 1 (p=0.07) and wk 3 (p=0.1); M had a higher BP than F at wk 2 (p=0.03). At all time points, females had more Tregs than males, and males had more Th17 cells (effect of sex: p<0.05 for all comparisons). Neither Tregs nor Th17 cells were altered vs. control following 1 wk of DOCA treatment (effect of treatment: p=0.9 for both). After 2 wks of DOCA treatment, Tregs decreased in treated males vs. control but were maintained in females (interaction: p=0.06) and Th17 cells increased in both sexes, although the increase was greater in males (effect of DOCA: p<0.001; interaction: p=0.02). Finally, at wk 3 of treatment, DOCA increased Tregs (effect of DOCA: p<0.01) and Th17 cells (effect of DOCA: p=0.03) in both sexes. We propose that the sex‐specific effects of DOCA on T cells at wk 2 contribute to sex differences in BP. The ability of females to maintain Tregs and thereby limit increases in effector Th17 cells at this time point may be a critical pathway by which they are able to maintain a lower BP relative to males.Support or Funding InformationR01HL127091‐02

Male Control
Male DOCA
Female Control
Female DOCA

Tregs: Wk 1
4±0.5
4±0.6
5±0.6
5±0.5

Tregs: Wk 2
5±0.8
3±0.5*
6±0.9
7±0.7

Tregs: Wk 3
2±0.3
4±0.3*
4±0.5
7±0.6*

Th17 cells: Wk 1
16±2
17±1
11±1
11±1

Th17 cells: Wk 2
6±0.6
27±3*
4±0.5
17±1*

Th17 cells: Wk 3
17±1
21±3*
11±2
17±3*

All data are expressed as percent of CD3+CD4+ cells;
indicates p<0.05 vs. same sex control.
Sex chromosome complement involvement in vasopressin gene expression induced by water deprivation
Authors: Dadam Florencia , Mecawi André , Cambiasso M.Julia , Antunes‐Rodrigues José , Vivas Laura , Caeiro Ximena E. 
Published: November 2023

Vasopressin (AVP) is involved in the control of blood pressure and water balance. Basic and clinical data suggest there are sex differences in the expression and function of AVP that cannot be entirely explained solely as a result of gonadal steroid action. This study aimed to define whether sex chromosome complement (SCC) may differentially modulate sex differences in the vasopressin gene expression in response to osmotic stimulation.In order to evaluate whether SCC may differentially modulate vasopressin gene expression we used mice of the “four core genotype” model, in which the effect of gonadal sex and SCC are dissociated, allowing comparisons of sexually dimorphic traits between XX and XY females as well as in XX and XY males. Comparing these genotypes, it is possible to segregate the role of a) SCC (comparing mice with the same gonadal type but different SCC: XX vs. XY) b) sex (females vs. male) and c) the interaction of SCC and sex.To remove the activational effects of sex hormones, that might mask the modulatory action of SCC and the organizational hormonal effects, mice were gonadectomized and 15 days later were submitted to a water deprivation protocol (DEP group). Control groups remained with access to water and normal diet (CON group). Twenty four hours later, brains and plasma of all groups were collected to assess plasma electrolytes and osmolality and to evaluate relative gene expression of AVP at the supraoptic (SON) and paraventricular nuclei (PVN).The statistical analysis showed a significant effect of treatment for both, osmolality and plasma Cl− levels {F(1,40)=4,91 p <0,05; F(1,39)=4,03 p <0,05 respectively, n=6/group.}, however no sex nor SCC effects were observed. On the contrary, a significant effect of the interaction of treatment and SCC factors was observed in the AVP genetic expression at SON {F(1,13)=5,91 p<0,05} n=3–4/group}. Regardless of sex (male or female) XY‐DEP mice (XY‐male and XY‐female) expressed higher AVP mRNA levels compared to XY‐CON animals. However, XX mice (both XX‐male and XX‐female) showed similar levels of AVP mRNA expression for both controls and deprived groups (XX‐CON and XX‐DEP). At the PVN no statistical significant differences were observed. These results reveal a modulatory effect of sex chromosome complement on water deprived AVP gene expression within the SON, what may underlie sex differences in the regulation of vasopressin secretion.Support or Funding InformationSupported by: ANPCyT, ISN, SECyT, Mincyt‐Cba, CnPq, CONICET.
Effect of Advanced Maternal Age on Cardiovascular Function in Adult Male and Female Rat Offspring
Authors: Shah Amin , Care Alison Sandra , Cooke Christy Lynn , Morton Jude Sally , Quon Anita , Kirschenman Raven , Davidge Sandra Thomas 
Published: November 2023

Pregnancy in advanced maternal age (< 35 yrs of age) increases the risk of immediate and long‐term health complications in mothers and offspring. Using a rat model of advanced maternal age, we have recently demonstrated poor fetal development, decreased litter size, and impaired maternal vascular function. The present study aimed to investigate the cardiovascular health of adult male and female offspring born to dams of advanced maternal age. Echocardiography and isolated working heart techniques were used to assess in vivo cardiac function and ex vivo cardiac function recovery after ischemia/reperfusion (I/R) respectively in 4 month and 12 month adult offspring born to young (4 month) or maternal aged (9.5 month) rat dams. At 4 month of age, ex‐vivo data showed that male offspring from aged dams had significantly decreased cardiac function recovery after I/R compared to offspring from young dams (45.78 ± 9.54% vs. 107.6 ± 4.03%; P< 0.001). In contrast, there was no significant difference in cardiac function recovery after I/R in female offspring born from aged vs young dams (87.6 ± 3.26% vs. 94.79 ± 5.89 %; P=NS); indicating better cardiac tolerance against I/R injury compared to their male counterparts. At 12 month of age, echocardiographic data revealed that compared to offspring from young dams, male offspring from aged dams developed in vivo cardiac diastolic dysfunction as indicated by decreased isovolumic relaxation time (male offspring IVRT; young dam 34.27 ± 2.04 vs. aged dam 27.61 ± 0.99 msec; P< 0.01). In contrast, there was no significant difference in in vivo cardiac function between the groups in female offspring indicating intact in vivo cardiac function. We further evaluated whether aging in the female offspring impacted ex vivo cardiac susceptibility to I/R. Our ex vivo data showed that 12 month old female offspring born from both young and aged dams had a similar basal cardiac power during the pre‐ischemia period and similar percent recovery of cardiac function after I/R injury (female offspring; young dam 102.8 % vs. aged dam 81.08 %, Mann‐Whitney U test: P=NS). In conclusion, aged male offspring born to mothers of advanced maternal age had an increased susceptibility to the development of cardiovascular dysfunction.Support or Funding InformationThis work is funded by grants from the Canadian Institutes of Health Research (MOP 133566), the Women and Children's Health Research Institute through the generous contributions of the Stollery Children's Hospital Foundation and the Royal Alexandra Hospital Foundation. A. Shah is supported by fellowship from the Molly Towell Perinatal Research Foundation Canada. S. Davidge is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health.