bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronically Increased Aldosterone In Vivo Attenuates Coronary Vasodilation to Adenosine
Authors: Khan Maloree , Brown Scott M. , Meuth Alex I. , Bender Shawn B. 
Published: June 2021

Adenosine‐induced coronary vasodilation is an important cardioprotective mechanism during cardiac hypoxia and ischemia and is utilized clinically for the determination of coronary flow reserve (CFR), an independent predictor of cardiac mortality. Impaired coronary vasodilation to adenosine is more common in diseases associated with inappropriate activation of the renin‐angiotensin‐aldosterone system (RAAS) and recent evidence indicates that systemic blockade of mineralocorticoid receptors (MR) improves CFR in patients with diabetes. The mechanisms underlying RAAS‐dependent attenuation of coronary adenosine‐induced vasodilation, however, remain unclear. Therefore, we hypothesized that chronic infusion of the MR agonist aldosterone would blunt coronary adenosine‐mediated vasodilation and that this would involve reduced adenosine type 2A (A2A) receptor‐dependent vasodilation. Studies were performed using 13–15 week old male C57BL/6J mice infused with either vehicle (95% EtOH in saline) or a subpressor dose of aldosterone (250 μg/kg/d) chronically for 4 weeks via osmotic minipump. After infusion, left ventricular coronary arteries were dissected and function was assessed by wire myography. Chronic infusion of aldosterone raised circulating aldosterone concentrations but did not increase heart weight. Aldosterone infusion blunted coronary vasodilation to adenosine, particularly within the range of adenosine concentrations relevant to those in vivo during cardiac hypoxia (1–10 μM), but did not reduce maximal adenosine‐induced vasodilation. Coronary vasodilation to the endothelium‐dependent vasodilator acetylcholine was also blunted by aldosterone infusion. Additional studies revealed that coronary adenosine‐induced vasodilation in the mouse is entirely dependent on activation of K+ channels and that selective activation of adenosine type 2B (A2B) receptors with BAY 60–6583 induces greater vasodilation that activation of A2A receptors with CGS‐21680. Chronic aldosterone infusion blunted coronary vasodilation in response to selective A2A, but not selective A2B, activation. RT‐PCR revealed no difference in aortic A2A and A2B gene expression. Taken together, our data demonstrate that chronic elevations of aldosterone blunt coronary vasodilation to adenosine via impaired A2A‐dependent vasodilation. This aldosterone‐dependent blunting of adenosine‐mediated vasodilation has implications for cardiac injury in response to hypoxia in states associated with inappropriate RAAS activation such as obesity and diabetes.Support or Funding InformationFunded by VHA BLR&D BX002030 (SBB) and a STRIDE Undergraduate Summer Research Fellowship (MK) supported by the American Physiological Society and NIH NHLBI R25 HL115473‐01.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation of microRNA 15b and Its Downstream Protein Targets in the Heart by Oral Ingestion of Beetroot Wine: Potential Protective Role against Doxorubicin Cardio Toxicity
Authors: Rehman Shabina , Talukder Jamil 
Published: June 2021

BackgroundBeetroot juice (BRJ) is a natural food product containing high levels of nitrate and antioxidant flavonoids/vitamins. Oral intake of BRJ protects against cardiotoxicity of doxorubicin (DOX) ‐ an anticancer drug. BRJ reduced serum cardiac troponin I and ventricular dysfunction caused by DOX and increased plasma nitric oxide (NO) levels. The present study aims at elucidating the effects of BRJ on microRNA 15b (miR15b) ‐ a key modulator of cellular bioenergetics and survival pathways and play an important role in cardiac ischemia‐reperfusion injury.Methods & ResultsAdult male CF‐1 mice were divided into 4 groups (n=3–4/group): 1) Saline [0.2 ml, IP]; 2) DOX [15 mg/kg, IP]; 3) BRJ [BRJ extract added in drinking water (10 g/L) for 13 days]; 4) BRJ+DOX ‐ mice ingested BRJ for 7 days before DOX injection and through the 5‐day post‐DOX period. Five days after DOX or saline injection, ventricular tissues were collected for real‐time PCR or Western blot assays. miR15b expression was significantly decreased in DOX‐treated hearts (Fig. A). BRJ intake not only enhanced the basal level of miR15b, but also completely prevented the depressive effects of DOX on miR15b. BRJ also significantly reduced the protein targets of miR15b ‐ Bcl‐2, but not Arl2 (ADP‐ribosylation factor‐like protein 2) and ANT1 (ADP/ATP translocase 1) (Fig. B, C). Interestingly, we also observed inhibitory effects of BRJ on Bax and NOSTRIN (endothelial nitric oxide synthase traffic inducer) (P<0.05), indicating its potential modulation on eNOS activity and NO production (Fig. B, C).ConclusionOral ingestion of BRJ significantly enhanced miR15b expression in the heart, which is associated with down‐regulation of several protein targets that may act in concert to affect the crucial cellular bioenergetics and survival processes deranged by DOX. These novel findings may help to understand the cardioprotective mechanisms of BRJ as an effective and safe dietary supplement in combating DOX cardiotoxicity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduction of Reperfusion Cardiac Injury in Donation After Circulatory Death Hearts Through Modulation of Electron Transport
Authors: Chen Qun , Toldo Stefano , Lesnefsky Edward , Quader Mohammed 
Published: June 2021

INTODUCTIONHeart transplantation (HT) is a valuable option to prolong life in an end stage heart failure (HF) patient, but this option is limited due to the availability of donor hearts, which currently come from brain death donors only. Expansion of the heart donor pool is urgently needed. One potential source of donor hearts is donation after circulatory death (DCD) donors. Since the DCD process involves substantial ischemia (ISC) and reperfusion (REP) injury to heart, strategies are needed to reduce cardiac injury in DCD hearts for HT.HYPOTHESISAmobarbital (AMO) give during REP decreases cardiac injury. Based on the current human DCD protocol, the duration of ISC prior to heart procurement varies from 25 to 40 min. Thus, we examined if AMO given at the onset of REP can decrease cardiac injury in DCD heart following 45 min of global ISC.METHODSAfter 45 min of ISC, DCD hearts received AMO (2 mM) at the onset of REP for 5 min followed by buffer perfusion for 55 min; or buffer perfusion only for 60 min. Cardiac injury was measured by the left ventricle (LV) infarct size. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria(IFM) were isolated at 10 min of REP to measure calcium retention capacity (CRC, nmol calcium/mg protein) to assess mitochondrial permeability transition pore (MPTP) opening and rate of oxidative phosphorylation (nAO/min/mg).RESULTSAMO given during REP decreased the infarct size by 35% compared to untreated hearts. AMO improved the CRC in both SSM and IFM (Table), indicating a decreased susceptibility to MPTP opening during early REP. AMO did not influence oxidative phosphorylation with either complex I (glutamate) or complex II substrates (succinate+rotenone), suggesting that the protection of AMO is not due to improved oxidative phosphorylation.CONCLUSIONModulation of mitochondrial respiration at REP is a potential strategy to decrease cardiac injury in DCD hearts through inhibition of MPTP opening.Support or Funding InformationScientist development grant (MQ) from American Heart Association, Merit Review Award ( 2IO1BX001355‐01 EJ), R21AG054975‐01 (QC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Increased expression of microRNA‐29b attenuates function of Ca2+‐activated K+ channels in human PASMC from idiopathic PAH patients
Authors: Babicheva Aleksandra , Ayon Ramon Jose , Makino Ayako , Yuan Jason X.‐J. 
Published: June 2021

IntroductionPulmonary artery smooth muscle cells (PASMC) isolated from patients with idiopathic pulmonary arterial hypertension (IPAH) exhibit a more depolarized membrane potential in comparison to PASMC from failed donor lung tissue. The development of sustained pulmonary vasoconstriction and vascular remodeling, depend, in part on the depolarized membrane potential. Changes in activity and/or expression of large‐conductance Ca2+‐activated K+ (BKCa) channels have a direct impact on the resting membrane potential of PASMC. Inhibition of BKCa channels is involved in the pathophysiology of IPAH by causing membrane depolarization and vasoconstriction due to elevated [K+]i that promotes enhanced Ca2+ influx through voltage‐gated Ca2+ channels. However, the underlying mechanisms responsible for downregulation of BKCa channels in IPAH‐PASMC remains unknown. MicroRNAs (miRNAs) serve as important post‐transcriptional regulators of gene expression by inhibiting translation and stability of mRNAs. We hypothesized that upregulation of miRNA‐29b inhibits BKCa channels in PASMC isolated from IPAH patients.MethodsPASMC from healthy subjects and patients with IPAH were used for this study. K+ currents, recorded using the conventional whole‐cell configuration of the patch clamp technique, were elicited by a series of depolarizing steps from a holding potential of −80 mV for 500 ms. The cell‐attached configuration of the patch clamp technique was used to measure single‐channel currents from BKCa channels. The activity of BKCa channels was also determined in normal PASMC overexpressed miRNA‐29b, and IPAH‐PASMC transfected with miRNA‐29b inhibitor. mRNA and protein of BKCa channels were quantified by qPCR and Western blot, respectively.ResultsUpregulated miRNA‐29b correlated with the decreased activity of BKCa channel in PASMC from IPAH patients. Expression of the pore‐forming subunit α (KCNMA1) is higher (7.9845±1.49, n=4, P<0.001) while that of the auxiliary subunit β1 (KCNMB1) is lower (0.1175±0.05, n=4, P<0.001) in IPAH‐PASMC compared to normal cells. Overexpression of miRNA‐29b in normal PASMC significantly attenuates BKCa channel current density (15.01±1.76 pA/pF, n=10) when compared to controls (100.18±8.53 pA/pF, n=10) at +80mV and downregulates KCNMB1. Inhibition of miRNA‐29b rescued BKCa currents (127.16±18.50 pA/pF, n=5) in IPAH‐PASMCs compared to negative controls (5.81±0.68 pA/pF, n=3) at +80mV and upregulates KCNMB1.ConclusionUpregulated miRNA‐29b results in posttranscriptional downregulation of KCNMB1 which leads to attenuation of BKCa channel activity in IPAH‐PASMC.Support or Funding InformationThis work was supported in parts by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL125208, HL126609, and HL135807).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intravascular pressure stimulates vasoconstriction through PKD2 channel SUMOylation in smooth muscle cells
Authors: Hasan Raquibul , Yin Wen , Bulley Simon , Leo Dennis , Jaggar Jonathan H. 
Published: June 2021

Polycystin 2 (PKD2) channels are expressed in smooth muscle cells of several vascular beds, including cerebral and mesenteric arteries and aorta. Physiological functions of PKD2 channels in the vasculature are unclear. Here, to better understand physiological functions of PKD2 channels in arterial smooth muscle cells, we investigated whether this protein undergoes post‐translational modification. Using arterial biotinylation, immunoFRET and inducible, smooth muscle‐specific PKD2 knockout (PKD2sm−/−) mice, our data show that PKD2 exists as two different molecular weight proteins that are primarily plasma membrane‐localized in arterial smooth muscle cells. Coimmunoprecipitation and immunoFRET imaging indicate that PKD2 is post‐translationally modified by SUMO1 (small ubiquitin‐related modifier), but not SUMO2/3, which produces the higher molecular PKD2 protein. Physiological intravascular pressure or depolarization, through the activation of voltage‐gated Ca2+ channels and extracellular CaV1.2 influx, stimulates PKD2 SUMOylation, which promotes surface localization. 2‐D08, a SUMOylation inhibitor, abolishes PKD2 SUMOylation and prevents pressure‐induced vasoconstriction, but does not alter depolarization (60 mM K+)‐induced vasoconstriction in arteries. Collectively, data indicate that intravascular pressure stimulates PKD2 SUMOylation, which promotes channel surface localization. Intravascular pressure then activates surface PKD2 channels, leading to vasoconstriction. Thus, pressure self regulates the myogenic response by controlling PKD2 channel SUMOylation in arterial smooth muscle cells.Support or Funding InformationNIH/NHLBIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of 5‐month interval walking training on cognitive function in elderly people
Authors: Furihata Mayuka , Morikawa Mayuko , Hayashi Ryoichi , Tomita Wayumi , Masuki Shizue , Nose Hiroshi 
Published: June 2021

AimsDeterioration of physical fitness with advancing age is suggested to be one of the major causes for dementia. We examined whether 5‐mo interval walking training (IWT) improved cognitive function with increased physical fitness in elderly.MethodsResidents >40 years old in Yurihonjo participated in this study. They were randomly divided into the control (CNT) and IWT groups. Subjects in the CNT group were instructed to maintain their sedentary lifestyle while those in the IWT group were instructed to perform IWT, repeating ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking (VO2peak), respectively, per day ≥4 days/week for 5 months from June to November, 2016. Before and after the intervention, we measured VO2peak and cognitive function with Urakami‐style Screening Test. Since 36 subjects dropped out during the intervention and additionally 24 subjects lacked ≥1 of the measurements, we analyzed the remaining 175 subjects (CNT, n=88 and IWT, n=87). Moreover, since subjects who marked ≤12 points in cognitive function were clinically defined as mild cognitive impairment, they were used for further analyses (CNT, n=17 and IWT, n=18).ResultsAfter the intervention, VO2peak and cognitive function increased by 3.0±1.1% and 3.5±3.0% in the IWT group, more than −2.0±1.3% and −7.1±2.9% in the CNT group, respectively (both, P<0.01), and these effects were enhanced in the mild cognitive impairment subjects; 5.8±2.3% and 34.1±8.7% in the IWT group vs −0.4±2.3% and 11.8±12.3% in the CNT group, respectively, (both, P<0.05).ConclusionThe five‐month IWT improved cognitive function with increased VO2peak in elderly, especially in the mild cognitive impairment individuals.Support or Funding InformationThis study was supported by a grant from by the Cabinet Office of Japan to re‐activate local communities which would lose their activity due to advanced aging.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in Cardiovascular Autonomic Activity and Reactivity in Essential Hypertensive Patients after Yogic Practices
Authors: Khadka Rita , Paudel Bishnu Hari , Karki Prahlad 
Published: June 2021

Globally prevalence of essential hypertension (EH) is increasing. It is one of the leading risk factors for global mortality. Several modifiable factors including overweight, obesity, physical inactivity contribute to the high prevalence rates of hypertension. Despite long‐term normalization of blood pressure by anti‐hypertensive drugs, there exists autonomic dysfunction. It is reported that yogic practices decrease BMI, BP and modify other risk factors in EH patients. We aimed to study whether combined easy yogic practices improve cardiovascular autonomic regulation both activity and reactivity in EH patients. Fifty essential hypertensive patients on similar pharmacotherapy were randomized into yoga (n=25, age 46.73±7.72 years) and control (n=25, age 46.1±7.01 years) groups. Yoga group practiced meditation, pranayama and few easy asanas for 40 min/day for one month. Control group did not practice yoga or any relaxation procedures. In both the groups cardiac autonomic activity was assessed using short‐term heart rate variability (HRV) by both time domain and spectral analysis, and reactivity using deep breathing (DBT), Valsalva Maneuver (VM), Handgrip (HGT) and Lying to standing (LST) tests before start of the study and after one month of the study. Institutional Ethical Committee approved the study. Age, BMI, BP, HR, and respiratory rate were comparable between both the groups before start of the study. The SBP (135.42 ± 15.5 vs 125.85 ±14.68, p=0.044), DBP (98.28 ± 12.95 vs 82.85 ± 10.09, p=0.019) and BMI (25.97 ± 2.96 vs 24.87 ± 2.70, p=0.039) decreased in yoga group after one month of yoga practice. Time domain measures of HRV, which are markers of cardiac parasympathetic activity [SDNN: 26.8(18.33.3) vs 35.2(26.87–38.3) ms, p=0.013; rMSSD: 25.2(8.95–33.3) vs 38.2(29.0–68.97) ms, p=0.024] increased in yoga group after yoga practice. Similarly, in spectral analysis, HF power [210(115.75–352.0) vs 400(141.0–518.25) ms2, p=0.0 46; Total power: 650.5(227.75–863.0) vs 862(634.5–1317), p=0.006] were increased in yoga group after yoga practice, whereas, there were no significant changes in markers of sympathetic activity; LF nu and LF/HF ratio after yoga practice. The E:I ratio (1.18 ± 0.08 vs 1.26 ± 0.09, p=0.003) and Valsalva ratio, which are indicators of parasympathetic reactivity also increased in yoga group after yoga practice. In conclusion, both parasympathetic activity and reactivity increased in EH patients after a month of yoga practice. It indicates that combined easy yoga practices improve cardiovascular autonomic regulation by increasing cardiac parasympathetic activity.Support or Funding InformationBPKIHS Research grantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EFFECTS OF PREVIOUS EXERCISE TRAINING ON PLASMA AND TISSUE NITRITE, AND CARDIOVASCULAR PARAMETERS IN RATS WITH PARKINSONISM INDUCED BY 6‐OHDA
Authors: Martins‐Pinge Marli Cardoso , de Jager Lorena , Amorim Eric Diego Turossi , Lucchetti Bruno Fernando Cruz , Lopes Fernanda Novi Cortegoso , Crestani Carlos Cesar , Pinge‐Filho Phileno 
Published: June 2021

In Parkinson's disease (PD) in addition to motor symptoms, presents cardiovascular dysfunctions, such as postural hypotension and blood pressure lability. Studies have shown that physical exercise decreases the risk of developing PD, as well as slows its progression. During aerobic training, there is an increase in the peripheral production of nitric oxide (NO), as well as in then substantia nigra pars compacta (SNpc) of patients with PD. However, no study evaluating the effects of exercise on NO levels of PD and the alterations on mean arterial pressure (MAP) and heart rate (HR) after inhibition of NO synthase (NOS) by Nw‐nitro‐arginine‐methyl‐ester (L‐NAME) in animals submitted to prior physical training and induced parkinsonism with 6‐hydroxydopamine (6‐OHDA) have been performed. Trained (T) or sedentary (S) animals underwent stereotactic surgery for bilateral 6‐OHDA or vehicle microinfusion (Sham group) in the SNPc. After 6 days, the animals were catheterized (artery and vein) to record the baseline parameters, followed by inhibition of NOS by L‐NAME (10mg/kg). A nitrite dosage was performed in the aorta, heart and plasma. After 4 weeks of swimming, there was resting bradycardia in the trained groups (6‐OHDA T and Sham T) (p <0.05). There was no difference in the NO from plasma in the four groups. In the aorta, there was an increase of NO in the 6‐OHDA group (p <0.05) when compared to Sham S, and a decrease in 6‐OHDA T animals (p <0.05) when compared to 6‐OHDA S and Sham T. At the heart, there was an increase in NO in the Sham T in relation to the sedentary ones and a decrease of NO in the animals 6‐OHDA T in relation to Sham T (p <0.05). Administration of L‐NAME promoted an increase in MAP and a decrease in HR in all groups, presenting lower increases in MAP in 6‐OHDA animals. In the FC, the difference between groups was a consequence of physical training. The data suggest the involvement of different NOS isoforms on cardiovascular system activated after physical training and Parkinsonism by 6‐OHDA.Support or Funding InformationCapes (fellowship to Lorena de Jager)CNPq (Research fellowships to MCMP, CCC, and PPF)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventricular‐arterial Coupling in Prostate Cancer Patients Treated with Androgen Deprivation Therapy at Rest and During Exercise
Authors: Lovoy Garrett M. , Post Hunter K. , Banister Heather R. , Sutterfield Shelbi L. , Caldwell Jacob T. , Ade Carl J. 
Published: June 2021

IntroductionAndrogen‐deprivation therapy (ADT) in prostate cancer has been suggested to promote an unfavorable cardiovascular disease risk profile and long‐term cardiovascular mortality. Impairments in vascular structure (increased arterial stiffness) and function (decreased endothelial‐dependent dilation) are known to occur with ADT, however, it remains unknown if the changes in structure‐function relationship adversely impacts the interaction between ventricular and arterial systems. Ventricular‐arterial coupling is a measure of effective arterial elastance (Ea) and left ventricular end‐systolic elastance (Ees) and is a central determinant of cardiovascular performance and cardiac energetics. Therefore, this study sought to evaluate ventricular‐arterial coupling at rest and during submaximal exercise in prostate cancer patients with and without a history of ADT.MethodsTo date, 7 prostate cancer patients with (n=3) and without (n=4) a history of androgen‐deprivation therapy treatment have completed the study. Ea, Ees, and ventricular‐arterial coupling (Ea/Ees) were measured at rest and during supine submaximal exercise. A high Ea/Ees is reflective of a compromised interaction between ventricular and arterial systems. To minimize the effect of heart rate on each parameter submaximal exercise was performed at a work rate corresponding to a heart rate of 100 beats/min.ResultsAt rest Ea (ADT: 2.9±0.2 mmHg/mL; non‐ADT: 3.4±0.8 mmHg/mL; P=0.2), Ees (ADT: 3.2±1.9 mmHg/mL; non‐ADT: 3.6±0.6 mmHg/mL; P=0.2), and Ea/Ees (ADT: 0.79±0.39; non‐ADT: 0.97±0.30; P=0.5) were similar between ADT and non‐ADT groups. Ea was not different between groups during exercise (ADT: 7.0±1.1 mmHg/mL; non‐ADT: 6.6±0.6 mmHg/mL; P=0.3). Moderate‐intensity exercise‐induced increases in Ees trended to be decreased in the ADT group (ADT: 3.5±1.2 mmHg/mL; non‐ADT: 4.7±0.5 mmHg/mL; P=0.05). Ea/Ees was also higher in the ADT group during exercise compared to the non‐ADT group, but did not reach statistical significance (ADT: 0.93±0.16; non‐ADT: 0.77±0.16; P=0.1).ConclusionsThe findings from this study provide preliminary data that indicates ADT in prostate cancer patients may adversely alter left ventricular end‐systolic elastance during exercise, but does not significantly alter ventricular‐arterial coupling. Additional data will contribute to the evaluation of the interaction between ventricular and arterial systems in patients receiving ADT.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.