bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic Hemodynamics and Cognition in Women with a History of Hypertensive Pregnancy
Authors: Miller Kathleen B , Fields Julie A , Harvey Ronée E , Lahr Brian D , Joyner Michael J , Miller Virginia M , Barnes Jill N
Published: November 2023

A history of hypertensive disorders of pregnancy, including preeclampsia, place women at an elevated risk of developing hypertension and cognitive impairments as they age. The purpose of this study was to determine if aortic hemodynamics were related to cognition in postmenopausal women with a history of hypertensive disorders of pregnancy. We evaluated 33 postmenopausal women with a history of preeclampsia (PE: age = 59 ± 5 y; BMI = 29 ± 5 kg/m2; years since last pregnancy = 35 ± 3 y) and 29 postmenopausal women with a history of normotensive pregnancy (NTP: age = 59 ± 5 y; BMI = 26 ± 5 kg/m2; years since last pregnancy = 35 ± 3 y). Participants underwent a cognitive testing battery including letter‐number sequencing, trail making test B, letter fluency, and category fluency tests to evaluate executive functioning and working memory. Mean arterial pressure (MAP) was measured with a brachial blood pressure cuff. Applanation tonometry (SphygmoCor) was used to derive the aortic pressure waveform and calculate aortic systolic blood pressure (ASBP), aortic diastolic blood pressure (ADBP), augmentation index (AI), and augmented pressure (AP). There were no differences in cognitive scores between groups (p > 0.05). Brachial blood pressure (MAP: 103 ± 2 vs. 103 ± 3 mmHg) and aortic hemodynamic measures (ASBP: 123 ± 3 vs. 121 ± 3 mmHg; ADBP: 78 ± 2 vs. 77 ± 2 mmHg; AI: 31 ± 2 vs. 28 ± 1 %; AP: 17 ± 1 vs. 15 ± 1 mmHg) were also similar between PE women and NTP women, respectively (p > 0.05 for all). There were no associations between measures of aortic hemodynamics and cognitive scores in women independent of their pregnancy history (p > 0.05). When evaluating these relationships within each group, ADBP was significantly associated with worse scores for letter‐number sequencing and letter fluency in PE women (r = −0.433 and r = −0.441, respectively, p < 0.05). Taken together, our results indicate aortic hemodynamic measures are not associated with cognition in middle‐aged postmenopausal women with different pregnancy histories; however, future studies should address the influence of elevated aortic hemodynamic variables and the longitudinal change in cognitive function in postmenopausal women with different pregnancy histories.

Support or Funding Information

NIH AG44170, NIH 118154
Pilot Study: Effects of Short‐term Summer School Program on Plasma Cognitive Marker and Non‐lipid Cardiovascular Risk Factors in Female Adolescents
Authors: Choi Myung Dong , Park Kyung‐Shin
Published: November 2023

Education and health are the most important in school‐aged children and adolescents. It is well known that physical activity is a crucial component of health promotion and academic achievement in youth. However, schools do not provide recommended amount of physical activity during regular school seasons. It was reported that especially children in low socio‐economic status (SES) communities have poorer physical health and lower academic performance than children higher in SES. Recent studies indicated that increased physical education in school improves academic achievement and physical health. Thus, this pilot study seeks to find further evidence for the role of extended summer school programs including physical activities in relation to biomarkers of cognition and cardiovascular health in the area of low SES communities.

PURPOSE

To determine the effects of short‐term summer school programs including 2‐hour exercise per day on a cognitive marker and non‐lipid cardiovascular risk factors in female adolescents.

METHODS

Thirty high school female students were recruited and 15 students were assigned to the summer school attendant group (SA) and completed summer school programs, including 2‐hour exercise daily for 5 weeks and 15 students were in non‐summer school attendant group (NSA). Plasma brain‐derived neurotrophic factor (BNDF), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) were measured immediately before and after summer vacation. One‐way ANCOVA was used to determine differences in BNDF, ICAM, and VCAM changes between the groups.

RESULTS

Plasma BNDF was elevated in SA group after summer vacation, compared with the NSA (12.8±2.2 ng/ml vs.10.0±1.7 ng/ml, respectively, P<0.001). Plasma ICAM level was decreased in the SA group after summer vacation, compared with the NSA (85.5±21.7 ng/ml vs. 109.2±25.9 ng/ml, respectively, P<0.001). Plasma VCAM was also decreased in the SA group after summer vacation, compared with the NSA (94.9±12.8 ng/ml vs. 109.5±18.4 ng/ml, respectively P<0.001).

CONCLUSION

Five‐week summer school program may have a positive influence on memory retention and also decrease systematic cardiovascular risk factors in female adolescents. Thus, these preliminary findings support that school‐aged adolescents, while attending at summer school programs, might have beneficial outcomes on brain's memory function and the cardiovascular health, especially in low socio‐economic status communities. However, this pilot study may not provide a direct relationship among BNDF, memory retention, and academic achievement. Thus, further study is needed to verify whether or not increased plasma BNDF improves academic performance and/or skills.
Amelioration of Sodium Fluoride‐induced hypertension, cardio‐renal oxidative stress and genotoxicity by Azadirachta indica through antioxidant and extracellular signal‐regulated kinase (ERK) 1/2 signalling
Authors: Adejumobi Olumuyiwa , Omobowale Temidayo , Oyagbemi Ademola , Ayenuro Olubukola , Ola‐Davies Olufunke , Adedapo Adeolu , Yakubu Momoh
Published: November 2023

In this study we investigated the protective effect of Azadirachta indica on sodium fluoride‐induced hypertension, oxidative stress, cardio‐renal toxicity and genotoxicity.

Sixty rats were used in this study. They were divided into six groups each containing 10 rats. Group A served as the controls and they received distilled water only for a period of 14 days. Group B rats were administered distilled water only for the first 7 days and thereafter, sodium fluoride was adminstered at 600ppm in drinking water for another 7 days. Rats in groups C and D were pre‐treated with the methanolic extract of AI for the first 7 days alone at the dosages of 100mg/kg and 200mg/kg respectively and thereafter administered NaF at 600ppm in drinking water for 7 days. In groups E and F rats, distilled water alone was given to the rats during the first 7 days while 100mg/kg and 200mk/kg respectively of AI was co‐administered with NaF for another 7 days. At the termination, blood pressure measurement, electrocardiogram, antioxidant status and ERK 1/2 signaling were evaluated.

Administration of NaF caused a significant (p<0.05) increase in systolic, diastolic and mean arterial blood pressure values relative to the control. Markers of oxidative stress such as myeloperoxidase, xanthine oxidase, malondialdehyde and hydrogen peroxide were significantly (p<0.05) increased relative to the controls. In addition, significant (p<0.05) decreases in the cardiac and renal contents of nitric oxide, protein and non‐protein thiol and reduced glutathione were also observed. Antioxidant, the activities of antioxidant marker enzymes; glutathione peroxidase, catalase and superoxide dismutase in both cardiac and renal tissues were significantly (p<0.05) decreased when compared with the control group. Treatment with NaF had no significant effects heart rate, QT and QTc (Bazett) values. NaF treatment also caused resulted in a reduction in the expression of Extracellular Regulated Kinase (ERK) 1/2 in both cardiac and renal tissues of treated rats. Genotoxicity studies showed that NaF treatment group elicited a significant (p<0.05) increase in the number of micronucleated polychromatic erythrocytes (MNPCE) in bone marrow when compared with the control group but this was ameliorated by treatment with AI.

From this study, it can be concluded that treatment with AI conferred a protective effect NaF‐induced hypertension, oxidative stress, cardiorenal toxicity and genotoxicity through antioxidant and ERK 1/2 signaling in rats.

Support or Funding Information

None
Cardiovascular System Explained on the Bases of Sports, Taught by Undergraduate Students Majoring in Biomedical Sciences or Biology
Authors: Lopez Hector , Hernandez‐Velez Maria
Published: November 2023

This year, Texas A & M University‐Kingsville (TAMUK) hosted, for the first time, a Physiology Understanding Week (PhUn week). This was the first time this initiative is held anywhere south of San Antonio, Texas. We had participants from two local middle schools. Undergraduate students from TAMUK engaged in presentations that taught middle school students how the circulatory system functions and showed its importance. We involved the children in physical activities, and provided hands on demonstrations to represent functions of the heart, like heart rate. We presented our information to over five groups of children, each group containing at least twenty kids. After the presentations were over, the children had a growing curiosity over human anatomy and physiology beyond the cardiovascular system. They asked questions related to all organ systems and different conditions that affect the human body. With this activity, we were able to introduce children of different grade levels to human physiology. By doing this, we peaked their interest at a young age, and encouraged them to look into a future career in the medical/health field.
Simvastatin Inhibits Myocardial Apoptosis through Targeting miR‐15a‐5p undergoing Cardiac Surgery
Authors: Ou Zhi‐Jun , Zhou Li , Liu Xiang , Li Yan , Xu Zhe , Zhang Xi , Xu Ying‐Qi , Wang Zhi‐Ping , Ou Jing‐Song
Published: November 2023

We previously demonstrated that simvastatin inhibited myocardial apoptosis in patients undergoing cardiac surgery. MicroRNAs play an important role in inhibiting myocardial apoptosis. Whether simvastatin inhibitis myocardial apoptosis by regulating microRNAs remain unknown. 70 patients undergoing cardiac surgery, 35 from simvastatin group and 35 from control group, were enrolled. Simvastatin (20mg) was administered preoperatively for 5–7 days. Myocardial tissues biopsies were taken before and after surgery. microRNAs array was performed. Some of up or down expression of microRNAs were validated by real‐time PCR. The expression of proteins related to apoptosis and the up or down expression of microRNAs were detected. Some mRNAs were also detected by real‐time PCR and luciferase assays was performed. microRNAs expression profiling revealed that 317 miRNAs were differently expressed in the normal heart tissue, control and simvastatin group. Simvastatin significantly down‐regulated 94 miRNAs and up‐regulated 41 miRNAs. Among of them, miR‐15a‐5p was significantly decreased by simvastatin, which was validated by qPCR analysis. MiR‐15a‐5p was predicted to target Bcl‐2 mRNA on the position of 2529–2536 nucleotides. Coincident with the change of miR‐15a‐5p, the mRNA expression of Bcl‐2 were increased in simvastatin group. The protein expression of Bcl‐2 was upregulated in simvastatin group before surgery. These findings demonstrated that simvastatin inhibited myocardial apoptosis undergoing cardiac surgery, at least in part, by targeting miR‐15a‐5p/Bcl‐2 pathway.

Support or Funding Information

National Natural Science Foundation of China (81170271, 81370370, 81500215, 81600382, 81670392 and Distinguished Young Scholar 81325001), the Changjiang Scholars Program from Ministry of Education of China, the Guangdong Pearl River Scholars Program, International Cooperation Project (2015DFA31070) from the Ministry of Science and Technology of China, Guangdong Natural Science Fund Committee, China (2015A030312009), Sun Yat‐Sen University Clinical Research 5010 Program; Program of National Key Clinical Specialties, The five and five projects from The First Affiliated Hospital, Sun Yat‐sen University.
Pharmacological cardiac sympathetic afferent denervation in pacing‐induced heart failure
Authors: Senador Danielle , Kaur Jasdeep , Sala‐Mercado Javier A , Krishnan Abhinav C , Alvarez Alberto , Hanna Hanna W , Lovelace Abe T , Rasaiah Megan M , Altamimi Yasir H , O'Leary Donal S
Published: November 2023

Chronic sympathoexcitation is a hallmark of congestive heart failure. Enhanced input from the cardiac sympathetic afferent reflex (CSAR) appears to be a major contributor to augmented central sympathetic outflow in heart failure (HF) in rats (Myocardial ischemia model. Wang et al., Hypertension, 2014) and dogs (Rapid ventricular pacing model. Wang and Zucker, Am. J. Physiol., 1996). Transient receptor potential vanilloid 1 (TRPV1) expressing cardiac afferent fibers are responsible for CSAR activation, since systemic (Zahner et al., J. Physiol., 2003) and epicardial (Wang et al., Hypertension, 2014) administration of resiniferatoxin (RTX), an ultra‐potent analog of capsaicin that degenerates TRPV1‐expressing neurons, can almost completely abolish CSAR activation in rats. We tested whether epicardial application of RTX degenerates cardiac sympathetic TRPV1‐expressing neurons therefore reducing CSAR reactivity, in canines with pacing‐induced HF. In control studies, stimulation of left ventricular afferents containing TRPV1 via topical application of capsaicin (2 mg/ml) caused a pressor response and tachycardia (Δ=+15 mmHg, +44bpm). These responses were abolished by acute topical application of RTX (50 μg/mL). Experiments were repeated 9 weeks following RTX treatment and the subsequent induction of HF via rapid ventricular pacing. RTX pretreatment abolished the responses to capsaicin, whereas CSAR was preserved in HF if no RTX pretreatment was performed. TRPV1 expressing neuronal degeneration was evaluated through immunofluorescence histology (IFH) in left ventricle tissue samples, with triple labeling for DAPI (nuclei marker), PGP9.5 (nerve terminal marker,) and TRPV1 receptors. RTX treated tissue samples showed considerably lower TRPV1 positive staining when compared to non‐treated samples. The present study validates RTX as a potential therapeutic method to block excessive CSAR activation in pacing‐induced heart failure dogs, therefore expanding pharmacotherapy options for heart failure

Support or Funding Information

NIH HL55473 and HL126706
Altered Arterial Baroreflex ‐ Muscle Metaboreflex Interaction in Heart Failure
Authors: Kaur Jasdeep , Senador Danielle , Krishnan Abhinav C. , Alvarez Alberto , Hanna Hanna W. , O'Leary Donal S.
Published: November 2023

Previous studies have shown that heart failure (HF) alters the strength and mechanisms of both the muscle metaboreflex and the arterial baroreflex during dynamic exercise. Muscle metaboreflex activation (MMA) in normal individuals increases mean arterial pressure (MAP) virtually solely by an increase in cardiac output (CO) whereas in HF, the mechanisms of this pressor response shift to peripheral vasoconstriction. In contrast, the pressor response evoked by baroreceptor unloading in normal subjects occurs primarily through peripheral vasoconstriction which is blunted in HF. How HF alters the interaction between these two powerful reflexes when activated simultaneously is unknown. We hypothesized that co‐activation of both reflexes in HF would cause a smaller increase in MAP and a larger vasoconstriction of the ischemic hindlimb vasculature, resulting in an attenuated restoration of blood flow to the ischemic muscle than that observed prior to HF. We activated the muscle metaboreflex in chronically instrumented canines during mild exercise (via graded reductions in hindlimb blood flow; HLBF) followed by baroreceptor unloading (via bilateral carotid occlusion; BCO) before and after induction of HF in the same animals. We observed that interaction between the two reflexes in normal animals is intimately dependent on the hemodynamic parameter investigated; MAP, conductance of all vascular beds except hindlimbs, and ventricular function all exhibited additive interaction, CO and renal conductance demonstrated occlusive interaction while HR exhibited facilitative interaction. Furthermore, BCO during MMA caused a preferentially larger vasoconstriction in non‐ischemic vascular beds, thereby redirecting blood flow to the ischemic vascular bed. However, after induction of HF, all cardiovascular responses except ventricular function exhibited occlusive interaction in response to baroreceptor unloading during MMA. The pressor response during co‐activation of reflexes occurred via substantial vasoconstriction of all vascular beds including the ischemic active muscle and there is no significant restoration of blood flow to the ischemic vascular bed. We conclude that larger vasoconstriction of ischemic active skeletal muscle during co‐activation of both reflexes in HF attenuates the restoration of blood flow to ischemic muscle.

Support or Funding Information

HL‐55473 and HL‐126706
Increased CVD Risk Burden Diminishes the Protective Effect of Remote Ischemic Preconditioning Against Endothelial Ischemia‐Reperfusion Injury in Humans
Authors: Van Guilder Gary P. , Trachte Tiffany
Published: November 2023

Purpose

A powerful treatment against endothelial ischemia‐reperfusion injury is remote ischemic preconditioning, which can trigger tissue protection by exposing a limb to small cycles of vascular occlusion. However, animal models of aging, diabetes, hyperlipidemia, and obesity indicate that the protective benefits of ischemic preconditioning are weakened. The extent to which a clinically relevant burden of CVD risk factors interferes with remote preconditioning in humans is not clear. The purpose of the present study was to determine the influence of CVD risk factor burden on the capacity of remote ischemic preconditioning to prevent endothelial reperfusion injury in adults.

Methods

Twenty‐two (age: 45±14 yr) sedentary adults (12 lower burden: 0–2 risk factors; <1% 10‐year FRS; 10 raised burden: 3–5 risk factors: ≥1% 10‐year FRS) were studied using a 2×2 randomized cross‐over design. Digital arterial tonometry (EndoPAT 2000, Itamar Medical Inc.) was used to assess endothelial vasodilation during reactive hyperemia before and after 65 min of left arm endothelial ischemia‐reperfusion injury (20 min brachial artery ischemia followed by 45 min reperfusion) that was preceded by remote ischemic preconditioning (right arm brachial artery: 3×5 min ischemia/reperfusion) or sham. Experiments were conducted in accordance with the Declaration of Helsinki for protection of human subjects.

Statistical Analysis

Repeated measures ANOVA was used to assess group differences between the reactive hyperemia index (RHI) before and after endothelial reperfusion injury in the absence and presence of remote ischemic preconditioning.

Results

In lower burden subjects, remote preconditioning was able to prevent endothelial reperfusion injury (from baseline: 2.1±0.4 to post endothelial injury: 2.5±0.5, P=0.072). In contrast, in the raised burden subjects the RHI (baseline: 2.3±0.9) was significantly reduced by 25% despite attempts to induce protection by remote preconditioning (1.8±0.7; P<0.05). The capacity of remote ischemic preconditioning to protect against endothelial reperfusion injury was inversely related (r=−0.61; P=0.004) to CVD risk burden.

Conclusions

Endothelial reperfusion injury was prevented when preceded by remote ischemic preconditioning in the lower burden subjects but failed to provide protection in the raised risk burden subjects. CVD risk factors appear to disrupt the protective properties of remote ischemic preconditioning in humans. These findings provide important critical insight to explain why the large‐scale multi‐center RIPHeart and ERICCA randomized trials of remote ischemic preconditioning failed to show reductions in postoperative clinical events in patients undergoing elective cardiac surgery.
Age‐dependent Mitochondrial Targeting Of Protein Kinase C Epsilon In Cardioprotection
Authors: Kang Chen , Qin Jingping , Osei Wil , Hu Keli
Published: November 2023

Protein kinase C (PKC) has been shown to selectively translocate to mitochondria upon activation and is an important mediator in the cardioprotection against ischemia. Given that cardioprotection is age‐related, we aimed to determine the effect of aging on adenosine‐induced mitochondrial translocation of PKCɛ and its underlying mechanisms. Freshly isolated cardiomyocytes from the young adult (2 to 3‐month) and middle‐aged (10 to 12‐month) rat hearts were employed. Cells were pretreated with or without adenosine, adenosine plus DPCPX and stained with a mitochondria‐selective probe MitoTracker before mitochondrial fractionation. Intact mitochondria were obtained from cardiomyocytes by differential centrifugation and immunostained with the anti‐PKCɛ antibody. The quantification analysis was obtained from calculating the percentage of PKCɛ‐positive mitochondria over total mitochondria. We investigated whether selective PKCɛ translocation to mitochondria, a key step for cardioprotection against ischemia, is influenced by aging. Our data showed that adenosine‐induced translocation of PKCɛ was largely decreased in middle‐aged rats when compared to that in young adult rats. We also found out that the basal level of PKCɛ in cardiac mitochondria was significantly lower in middle‐aged rats than that in young adult rats. However, in both cardiac myocytes and rat heart derived H9c2 cells, adenosine treatment did not alter the expression of caveolin‐3, the protein that is important for the PKCɛ translocation to mitochondria. Further, Western blotting data suggest that the protein expression of mitochondrial import machineries HSP90 and TOM70 from middle‐aged rat hearts was prominently lower than that from young adult rat hearts. In conclusion, we demonstrate that adenosine‐induced translocation of PKCɛ to mitochondria is age‐related, possibly at least in part, through the regulation of HSP90 and TOM70 expression. These results point out an important role of mitochondrial import machineries in the cardioprotection with aging.
Longitudinal Strain by Speckle Tracking Imaging Detected Regional Myocardial Dysfunction in a Rat Model of Ischemia‐Reperfusion
Authors: Omoto Ana Carolina Mieko , Gava Fábio Nelson , Silva Hadder Batista , de Oliveira Mauro , Silva Carlos Alberto Aguiar , Salgado Helio Cesar , Fazan Rubens
Published: November 2023

The reperfusion therapy after acute myocardial infarction is frequently used for improving coronary blood flow. However, it is known that in long term, reperfused patients may develop heart failure. Echocardiographic follow‐up of reperfused patients has been important to detect cardiac abnormalities. Particularly, strain by speckle tracking has been an echocardiographic approach able to early detect areas of myocardial dysfunction. The aim of this study was to evaluate the endocardial longitudinal strain by speckle tracking in rats submitted to ischemia‐reperfusion (IR). IR consisted of ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion. Male Wistar rats were subjected by IR (N=12) or fictitious sham procedure (control, N=9) and were evaluated by echocardiography, under ketamine and xylazine (50mg/kg, 10mg/kg i.p.) anesthesia, after 4 weeks. Echocardiographic videos were obtained in the long axis, with later application of the software analysis of Strain (VevoStrain™ software, Vevo 2100, Visual Sonics) and calculation of the ejection fraction (EF), end‐systolic volume (ESV) and end‐diastolic volume (EDV), on bidimensional mode. The analysis of six myocardial segments revealed difference between groups only on basal anterior region (IR: −12.9 ± 1.8%, control: −17.8 ± 1.3%), and no difference on the other segments: basal posterior (IR: −15.9 ± 3.5%, control: −15.3 ± 2.6%); mid‐posterior (IR: −21.7 ± 3.3%, control: −22.6 ± 2.6%); apical posterior (IR: −23.9 ± 4.2%, control: −25.4 ± 2.8); mid‐anterior (IR: −9.5 ± 1.8%, control: −14.1 ± 2.8%); apical anterior (IR: −16.5 ± 3.3% control: −18.3± 1.6%). There was a reduction in the ejection fraction and an increase in the end‐systolic volume in the IR group (EF: 58.2 ± 4%, ESV: 303.2 ± 46uL) when compared with control group (EF: 74.6 ± 2%, ESV: 133.8 ± 18.7uL). There was no difference in the end‐diastolic volume (IR: 688.7 ± 56.5uL, control: 579 ± 53.7uL). In conclusion, it was found that the evaluation of strain by speckle tracking in a rat model of IR was useful for detecting regional abnormalities in myocardial deformation (as seen in basal anterior region). Future investigations using this technique before four weeks would be important to detect early abnormalities through the speckle tracking in reperfused ischemic myocardium.

Support or Funding Information

FAPESP and CNPq.
Sympathetic Function During Whole‐Body Cooling is Altered in Hypertensive Adults
Authors: Greaney Jody L , Kenney W. Larry , Alexander Lacy M.
Published: November 2023

Acute cold exposure activates the sympathetic nervous system and elicits a robust systemic pressor response. In hypertensive adults (HTN), cardiovascular‐related morbidity and mortality peak during cold winter months; however, the mechanisms underlying this association are not well defined. We hypothesized that whole‐body cold stress would evoke exaggerated increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in HTN compared to normotensive adults (NTN). MSNA (peroneal microneurography), beat‐to‐beat BP (Finometer), and heart rate (HR; ECG) were measured continuously in 10 NTN (6 M/4 W; age 53±3 yrs; resting BP 125±3/79±1 mmHg) and 10 HTN (5 M/5 W; age 57±2 yrs; resting BP 149±6/88±3 mmHg) during whole‐body cooling‐induced reductions in mean skin temperature (Tsk; water‐perfused suit) from 34.0 to 30.5°C. MSNA at 34.0°C was not different between groups (NTN: 51±4 v. HTN: 54±5 bursts· (100 heartbeats)−1; P=0.71). During cooling, the increase in MSNA was exaggerated in HTN (NTN: Δ = 8±3, HTN: Δ = 19±3 bursts· (100 heartbeats)−1; P=0.02). The cooling‐induced increases in both systolic BP (NTN: 9±3, HTN: 19±3 mmHg; P=0.03) and mean arterial pressure (NTN: 6±2, HTN: 10±2 mmHg; P=0.08) were greater in HTN. The HR response to cooling was not different between groups (P=0.16). The slope of the relation between MSNA burst incidence and diastolic BP did not change during cold stress in NTN (Tsk = 34.0°C: ‐4.0±0.7 v. Tsk = 30.5°C: ‐5.0±0.3 bursts· (100 heartbeats)−1·mmHg−1; P=0.17) but increased in HTN (Tsk = 34.0°C: ‐2.9±0.5, Tsk = 30.5°C: ‐5.0±0.4 bursts· (100 heartbeats)−1·mmHg−1; P=0.04). These data demonstrate that the whole‐body cooling‐induced increases in MSNA and BP are augmented in HTN. Further, sympathetic baroreflex sensitivity increases during cooling in HTN, but not NTN, presumably to allow for baroreflex‐mediated buffering of excessive cooling‐induced increases in BP. Collectively, these findings suggest that sympathetic function during cold stress is altered in human hypertension, likely contributing to increased cold‐associated cardiovascular risk.

Support or Funding Information

HL093238 (LMA) and HL120471 (JLG)
Modulation by NADPH‐ox/Rho‐kinase signaling of the cyclosporine‐NSAIDs interactions on blood pressure and baroreflexes in female rats
Authors: El‐Mas Mahmoud M , Ibrahim Karim S , El‐Yazbi Ahmed F , El‐Gowelli Hanan M
Published: November 2023

The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these adverse effects of CSA are influenced by co‐administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH‐ox/Rho‐kinase pathway mediates this interaction. Female rats were treated for 10 days with CSA (25 mg/kg/day), diclofenac (DIC, COX‐1/COX‐2 inhibitor, 1 mg/kg/day), celecoxib (COX‐2 inhibitor, 10 mg/kg/day), or their combinations. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), respectively, were constructed and slopes of the curve were taken as measures of BRS. Compared with control rats, CSA increased BP and reduced reflex chronotropic responses as indicated by the significantly smaller BRSPE and BRSSNP. Similar effects were observed in rats treated with diclofenac alone or combined with CSA. Whereas CSA hypertension was maintained after COX‐2 inhibition (celecoxib), the concomitant BRS reductions were largely eliminated. NADPH‐ ox inhibition by diphenyleneiodonium blunted the CSA/DIC‐evoked increases and decreases in BP and BRSPE, respectively. By contrast, fasudil (Rho‐kinase inhibitor) had no effect on CSA/DIC hypertension but reversed the associated reductions in both BRSPE and BRSSNP. Cardiac NADPH oxidase II (NOXII), but not Rho kinase (ROKII), protein expression was increased in CSA/diclofenac‐treated rats and this effect disappeared after co‐administration of fasudil or DPI. Together, depending on the nature of the cardiovascular response, NADPH‐ox and Rho‐kinase contribute variably to the worsened cardiovascular profile in CSA/DIC‐treated rats. Further, celecoxib rather than diclofenac could be a better choice as an add‐on therapy to CSA in autoimmune arthritic conditions.

Support or Funding Information

Supported by the ALEX‐REP Grant Fund, Alexandria University, Egypt (Grant HLTH‐13‐01).
Disorder of Renin‐Angiotensin System Promoting the Acute Pulmonary Inflammation by Particulate Matter 2.5 (PM2.5) Exposure
Authors: Lin Chung‐I , Wang Guan‐Hua , Cho Ching‐Chang , Wu Hsi Tien , Hsieh Wen‐Yeh , Lin Chih‐Sheng
Published: November 2023

Acute or chronic particulate matter 2.5 (PM2.5) exposure can induce oxidative stress, inflammation and pulmonary impairment by traversing the blood‐air barrier of alveolar and then depositing at lung. In the present study, we tested whether the pulmonary inflammation and impairment induced by PM2.5 exposure are related to the disorder of pulmonary renin‐angiotensin system (RAS).

In this study, we collected PM2.5 from waste gas which was produced from vehicle engine, and determined the component elements and structures of the PM2.5. The C57BL/6J (wild type, WT) mice and angiotensin converting enzyme II (ACE2) gene knockout (ACE2KO) mice were treated with the PM2.5 by intratracheal instillation once a day for a total of 3 days, and then sacrificed at the 4th day. Lung tissue of the mice was collected for the assays of molecular, biochemical and pathological changes to evaluate the acute pulmonary inflammation and lung injury induced by PM2.5 exposure.

The results indicated that the most of collected particulates in this study were aggregated and parts of them formed structure of chains below 2.5 μm diameter. The major compositions of the PM2.5 are carbon and oxide, and contain little silicon, sulfate and copper. The body weight of both WT and ACE2 KO mice treated with PM2.5 was decreased and resting breathing rate was significantly increased. PM2.5 treatment induced pathological leukocyte infiltration in the lung, increased pulmonary immunocytokines concentration, including interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α) and tumor growth factor beta 1 (TGF‐β1), and also promoted signaling protein ERK1/2 and STAT3 phosphorylation. The quantitative data showed that the levels of physiopathology and inflammation induced by PM2.5 were serious in the ACE2 KO mice compared with those in the WT mice. PM2.5 treatment significantly increased pulmonary ACE expression and activity in both WT and ACE2 KO mice. Interestingly, pulmonary ACE2 activity in the WT mice was also induced. We hypothesized that increased ACE2 activity in the WT mice is a physiological response for increased ACE activity due to PM2.5 exposure. However, the response is lack in the ACE2 KO mice because the mice being ACE2 deficiency. It is one of the reasons that serious physiopathology and inflammation induced by PM2.5 in the ACE2 KO mice compared with those in the WT mice.

Our data reveals that acute inflammation and lung injury could be induced by PM2.5 treatment. The disorder of pulmonary RAS may aggravate the disease progressive of pulmonary system due to PM2.5 exposure. Therefore, we propose that it may be helpful for the cardiopulmonary patients by RAS regulation when the patients are exposed to severe particulate pollutants.
Characterisation of a Mouse Kidney Cortical Collecting Duct Cell Line Suggests Plasticity Between Cell Types
Authors: Assmus Adrienne M , Mansley Morag K , Mullins Linda J , Peter Audrey , Mullins John J
Published: November 2023

The kidney collecting duct is composed of principal (PC) and intercalated (IC) cells responsible for the reabsorption of water and sodium, and the acid‐base balance, respectively. The immortalized mCCDcl1 cell line is widely used as a model for PCs since cells respond to glucocorticoid (MR) and mineralocorticoid (MR) hormones, such as aldosterone, and give reproducible electrophysiological responses.

The effect of culture media on sodium transport in the mCCDcl1 cell line was tested by electrophysiological methods and immunostaining. The cells were cultured on filters in two media: the original medium published by Gaeggeler et al.(2005), and an alternative medium using a different source of sodium selenite supplement (Gibco). The cells transepithelial voltage and resistance across monolayers of cells was measured using an epithelial volt‐ohm‐meter, allowing calculation of the equivalent short circuit current by Ohm's law. Basal currents recorded from cells cultured in the original medium measured −9.97μA/cm2, were amiloride‐sensitive and stimulated by ~2.6 fold following aldosterone treatment (−26.78μA/cm2). Cells cultured in the alternative medium exhibited negligible current and no response to aldosterone was observed.

Immunostaining was performed in the alternative media on the mCCDcl1 cells and on isolated subclones using antibodies against PC and IC markers: Aquaporin 2 (Aqp2) and the alpha subunit of the epithelial sodium channel (α‐ENaC) for PC, Connexin 30 (Cx30) and vacuolar H+ ATPase (V‐ATPase) for IC. Both the original cell line and the clonal sub‐lines exhibited varied expression of Aqp2 and Cx30, with evidence of co‐expression in sub‐populations of cells. 41.8% of cells from the parental sub‐line express both PC and IC markers whilst 23.8 to 58.7% cells in the clonal sub‐lines express both PC and IC markers. Expression of both PC and IC markers was confirmed by PCR analyses, and RNA sequencing. Immunostaining for α‐ENaC revealed staining across the apical membrane of the cells when cultured in the original medium and perinuclear staining when cells were cultured in the alternative medium.

These results show that the provenance of the culture media supplements has a direct consequence on the phenotype of the cells and correlates with their capacity for sodium transport. Secondly, mCCDcl1 cells can present characteristics of both principal and intercalated cells and may have the capacity to switch between the two phenotypes.

Support or Funding Information

British Heart Foundation Center of Research Excellence PhD Studentship
Predicting regression of a Ductus Arteriosus
Authors: Hussain Juzar , Ahmed Humza A. , Grant William A. , Hernandez Michelle D. , Quick Christopher M. , Stewart Randolph H.
Published: November 2023

The ductus arteriosus (DA) is a shunt connecting the pulmonary artery to the aorta allowing blood to bypass the lungs in a fetus. Although radius is a key variable that is correlated with incidence of patency, the primary mechanical properties of the shunt and the cardiovascular system that impact the regression of the DA after birth remain unknown. However, similar instabilities have been identified in blood vessels using mathematical modeling. Because sustained decreases in endothelial shear stress causes vessels to grow narrower, under the right conditions, vessels in a vascular network can enter a positive feedback loop. Decreases in flow yield decreased radii, which in turn increases resistance to flow. We therefore hypothesized that the patency and spontaneous regression of the DA is a manifestation of adaptation to shear stress, leading to equilibrium radii that may be stable or unstable. We first assumed the standard minimal closed‐loop model, which consists of two ventricles, four vascular compartments, and pulmonary and systemic resistances. We then assumed a shunt where blood flow and endothelial shear stress were governed by Poiseuille's Law. This resulted in a prediction that endothelial shear stress is a complex function of radius, but has a similar form to shear stress in a vessel within a vascular network. Assuming that the shunt remodels so that radius increases linearly with endothelial shear stress yields two potential equilibrium radii, the smaller of which is inherently unstable. This model not only provides a mechanism to explain shunt patency, but also predicts which combinations of parameters would predispose regression when the shunt constricts below a critical, unstable radius. Furthermore, by performing a simple sensitivity analysis, critical parameters are identified that can predispose shunts to spontaneously regress. Taken together, the present work provides critical insights into risk factors and potential medical treatments for patent ductus arteriosus.
Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain
Authors: Li Minghua , Suchland Katherine L , Ingram Susan L
Published: November 2023

The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM but it is not known if this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA‐treated rats compared to naïve rats. The reduction in CFA‐treated rats correlated with decreased CB1 receptor protein expression and function in the RVM. Paradoxically, the non‐selective CB1/CB2 receptor agonist WIN55,212 inhibited GABAergic mIPSCs in both naïve and CFA‐treated rats. However, WIN55,212 inhibition was reversed by the CB1 receptor antagonist rimonabant in naïve rats but not in CFA‐treated rats. WIN55,212‐mediated inhibition in CFA‐treated rats was blocked by the CB2 receptor‐selective antagonist SR144528 indicating that CB2 receptor function in the RVM is increased during persistent inflammation. Consistent with these results, CB2 receptor agonists, AM1241 and GW405833 inhibited GABAergic mIPSC frequency only in CFA‐treated rats and the inhibition was reversed with SR144258. When administered alone, SR144528 and another CB2 receptor‐selective antagonist AM630 increased mIPSC frequency in the RVM of CFA‐treated rats indicating that CB2 receptors are tonically activated by endocannabinoids. Our data provide evidence that CB2 receptor function emerges in the RVM in persistent inflammation and that selective CB2 receptor agonists may be useful for treatment of persistent inflammatory pain.

Support or Funding Information

These studies were supported by the grants from NIH (DA035316 and R56NS093894), and America Heart Association (13SDG14590005, MH.L.).
Does Mozart's music have a relaxation effect?
Authors: Hoshi Junko , Sasaki Mako , Sugawara Misaki , Yang Hongxia , Bao Sarina , Tannno Hiromasa , Kanno Emi , Maruyama Ryoko
Published: November 2023

Background

Previous studies have suggested that Mozart's music has a relaxation effect. In contrast, several studies have also reported that Mozart's music has an effect on enhancing the ability to focus. There is currently no consistent evidence demonstrating the effects of Mozart's music.

Objective

The purpose of this study was to evaluate the effects of Eine Kleine Nachatmusik (K.525), a piece representative of Mozart's music, on heart rate (HR), blood pressure (BP), and autonomic nerve activity.

Method

We performed electrocardiographic (ECG) measurements in 15 healthy young Japanese adults, aged between 19 and 24 years. None of the participants had received a specialized music education. We investigated BP and heart rate variability (HRV) in a resting state, when taking a reading‐span‐test (RST), and when listening to music. We used high frequency (HF, 0.15–0.40 Hz) components as an index of parasympathetic nerve activity and the ratio of low frequency (LF, 0.04–0.15 Hz) to HF components (LF/HF) as an index of sympathetic nerve activity. After 5 minutes at rest, a reading‐span‐test (RST) was used to place a load on participants. Then, participants used headphones to listen to K.525 and a favorite song chosen from 6 pieces of popular Japanese music in randomized order. Both K.525 and the chosen favorite song were approximately 6 minutes long. After listening to music, ECG measurement continued for 5 minutes. All data are expressed as mean ± SE. One‐way repeated‐measures ANOVA and multiple comparison tests were performed to compare each index. A value of P < 0.05 was considered significant.

Results

There was a significant decrease in HR but no significant changes in BP or LF/HF after listening to both K.525 and the favorite song. HF showed a significant increase when listening to the favorite song, whereas K.525 had no notable effect.

Conclusion

We found that Mozart's music has no relaxation effect. We suggest that a favorite song has a greater activation effect on parasympathetic nerve activity.

Support or Funding Information

This work was supported, in part, by a Grant‐in‐aid for Scientific Research (B) (25305018) from the Japan Society for the Promotion of Science.
Autonomic Dysregulation in Adolescent Concussion: Characterization and Temporal Resolution of Neurological Outcomes
Authors: Balestrini Christopher S. , Moir M. Erin , Abbott Kolten C. , Johnson Marjorie , Fischer Lisa K. , Fraser Douglas D. , Shoemaker J. Kevin
Published: November 2023

Although incidence is at epidemic levels, objective indicators of neurologic damage in adolescent concussion remain poorly described. Autonomic markers such as heart rate variability (HRV) have provided equivocal results; however, these predominantly are made under conditions of minimal physiologic stress. The current investigation employs postural stressors to examine underlying neurological outcomes associated with acute concussion and clinical recovery to test the hypothesis that concussion impairs dynamic autonomic adjustments in adolescents. We examined concussed adolescents (CONC; n = 35; 14 males; age 15 ± 1 yrs, range = 12–18 yrs) for up to 6 weekly visits from diagnosis. A group of age and activity level‐matched non‐concussed adolescents (CTRL; n = 35; 19 males; age 14 ± 2 yrs, range = 12–18 yrs) formed the reference control. HRV (root mean square of successive differences in R‐R intervals (RMSSD)) and heart rate were assessed during a sit‐to‐stand protocol (two trials of seated posture (three minutes), followed by two minutes of standing). Measurements were taken during the last minute of sitting and standing, the ten second period following the postural stress of standing, as well as the ten second period from maximum HR. While seated, RMSSD was lower in CONC (41 ± 24 msec) compared with CTRL (60 ± 40 msec; p < 0.05). 31 patients provided weekly data until clinical discharge. Compared with the first visit (43 ± 25 msec), seated RMSSD in CONC increased (51 ± 36 msec; p = 0.05) at the time of clinical discharge. Upon standing (10 seconds following postural change to standing), RMSSD was lower in CONC versus CTRL (13 ± 7 vs. 18 ± 12 msec; p < 0.05). Compared with the first visit, RMSSD following the induced postural stress did not improve in CONC over the six week recovery period. Following maximal HR, CTRL had increased RMSSD versus CONC (46 ± 30 vs. 34 ± 19 msec; p < 0.05). Compared with CTRL, seated HR was higher in CONC. This tachycardia effect persisted throughout the sit‐to‐stand protocol (78 ± 12 vs. 72 ± 12 bpm; p < 0.05) and was maintained until the time of clinical discharge (79 ± 13 vs. 72 ± 12 bpm; p < 0.05). In adolescent concussion, autonomic cardiac impairment is demonstrated by reduced RMSSD in the seated position and throughout the adjustment period in response to postural stress. Further, seated HR is increased following acute concussion and remains elevated by the time of clinical discharge. Seated HRV, but not HR, recovered to levels seen in the control population within three to six weeks. Thus, cardiac adjustments to modest postural stress may represent a measurable neurological impairment in adolescent acute concussion which can be objectively monitored throughout clinical recovery.

Support or Funding Information

Research supported by the Children's Health Research Institute (London, Canada).
L‐arginine Infusion Reduces Muscle Sympathetic Nerve Activity and Blood Pressure in Patients with Chronic Kidney Disease
Authors: Kaur Jasdeep , Vranish Jennifer R. , Fadel Paul J.
Published: November 2023

An overactive sympathetic nervous system is a known cardiovascular risk factor present in chronic kidney disease (CKD) patients. However, limited effort has been directed at identifying the mechanisms contributing to sympathetic overactivity in CKD. Herein, we examined a potential role for accumulation of the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) in driving the high sympathetic nerve activity (SNA) present in CKD. ADMA is elevated in CKD and is a strong, independent predictor of future cardiovascular events in these patients. Much of the work with ADMA has been correlational in nature with a focus on the well‐known vascular endothelial properties of nitric oxide. However, increasing functional evidence indicates that NO is also a key signaling molecule involved in the tonic restraint of sympathetic outflow from the brainstem. Thus, it is possible that NO synthase inhibition with elevated endogenous ADMA contributes to sympathetic overactivity in CKD patients. We tested the hypothesis that overcoming accumulation of endogenous ADMA with acute L‐arginine infusion reduces sympathetic overactivity in CKD patients. In 5 hypertensive CKD patients, muscle SNA (peroneal nerve microneurography), blood pressure (BP; finger photoplethysmography), and heart rate (ECG) were measured before, during, and 45 minutes after systemic intravenous infusion of L‐arginine, the natural substrate for NO synthase, at a dose of 250 mg/kg over 20 minutes. Following L‐arginine infusion, mean BP was reduced (111±4 mmHg, baseline vs. 105±4 mmHg, L‐arginine; P=0.009). Likewise, MSNA was significantly decreased with L‐arginine (70±4 bursts per 100 heart beats, baseline vs. 59±6 bursts per 100 heart beats, L‐arginine; P=0.023). The concomitant decrease in MSNA and BP strongly implicates a central sympathetic effect of L‐arginine. If L‐arginine was only restoring peripheral NO production, the endothelial‐mediated reduction in mean BP due to peripheral vasodilation would be accompanied by an arterial baroreflex‐mediated increase in MSNA. These preliminary findings of simultaneous reductions in MSNA and BP suggest that L‐arginine restores central NO production in CKD patients supporting a role for ADMA in mediating sympathetic overactivity and hypertension in CKD patients.

Support or Funding Information

NIH R01 HL127071