bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paeo‐tang attenuates disharmony between the heart and kidney in L‐NAME‐induced hypertension
Authors: Na Se Won , Hong Mi Hyeon , Kim Hye Yoom , Ahn You Mee , Yoon Jung Joo , Lee Yun Jung , Lee Ho Sub , Kang Dae Gill 
Published: June 2021

Hypertension has been approved to cause disharmony between the heart and kidney such as cardiac hypertrophy and kidney dysfunction. In traditional oriental medicine Paeo‐tang (PET) has been shown to have effects on blood circulation improvement. However, the beneficial effect of PET on hypertension remains unknown. In this study, we investigated that PET attenuates blood pressure and suppresses cardiac hypertrophy in NG‐nitro‐L‐arginine methylester (L‐NAME) rat model. Hypertensive rat models were induced by the administration of L‐NAME (40 mg/kg/day) and then PET (50 or 100 mg/kg/day) or Olmetec was treated for 2 weeks. PET treatment significantly suppressed the systolic blood pressure and decreased intima‐media thickness in the thoracic aorta. PET restored the L‐NAME‐induced decrease in aortic relaxation response to acetylcholine and atrial natriuretic peptide (ANP). However, PET didn't restore the aortic relaxation response to sodium nitroprusside. PET markedly restored the phosphorylation of endothelial nitric oxide synthase in aortic tissue. Heart weight and ANP mRNA expression in heart tissue were decreased by PET in a dose‐dependent manner. PET ameliorated the functional decline in the kidney such as albumin, blood urea nitrogen, creatinine. These results demonstrated that PET possesses vascular protective effects against L‐NAME‐induced hypertension. In addition, PET regulates harmony between the heart and kidney via inhibition of cardiac hypertrophy and renal dysfunction.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cardiovascular Effects Of Acute Optogenetic Modulation Of Oxytocin‐PVN Neurons
Authors: Mohammed Mazher , Tan Yalun , Harrison Caitlin Baumer , Scott Karen A , Sumners Colin , de Kloet Annette , Krause Eric G. 
Published: June 2021

The actions of oxytocin (OT), a neuropeptide that is largely synthesized in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus, has been implicated in a variety of homeostatic processes. Recent studies have demonstrated that chronic activation of OT neurons in the PVN prevents hypertension that is a consequence of intermittent hypoxia/hypercapnia. The present study combines genetically‐modified mice with in vivo optogenetics to determine the cardiovascular consequences of selective inhibition or excitation of OT neurons residing in the PVN. Male mice engineered to direct the expression of Cre recombinase to the OT gene had adenoassociated virus synthesizing an inhibitory opsin (Switch), an excitatory opsin (ChR2), or enhanced yellow fluorescent protein (eYFP) bilaterally injected into the PVN. Subsequently, mice were implanted with fiber optics targeting the PVN. One month later, mice were anesthetized with isoflurane and were implanted with a Millar catheter into their left common carotid artery for continuous recording of blood pressure and heart rate. Relative to the eYFP control group, OT‐Cre mice expressing Switch exhibited reduced blood pressure (−24±6 mmHg) and heart rate (−21±9 BPM) in response to optogenetic inhibition when compared with the eYFP group (4±2 mmHg and 5±4 bpm; n=3, p<0.05). In contrast, in the ChR2‐injected group, blue light stimulation (1 min; 30 Hz; 20ms pulse width) significantly increased blood pressure by 15±2 mmHg while decreasing heart rate by −27±10 bpm when compared to controls (0±1mmHg and 9±5 bpm; n=5, p<0.01. Neuroanatomical experiments revealed that neurons in the PVN that synthesize OT send dense axonal projections to the median eminence, the nucleus of the solitary tract, and the rostral ventral lateral medulla. Collectively, the results suggest that OT synthesizing neurons in the PVN mediate cardiovascular function possibly by affecting autonomic outflow and/or the activity of neuroendocrine axes.Support or Funding InformationNIH Funding supported the present studyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Fat Mass and Lean Mass on Blood Pressure Determinants in Healthy Young Men and Women
Authors: Connolly Kathleen , Middlemiss Jessica , Wilkinson Ian , McEniery Carmel 
Published: June 2021

BackgroundObesity is commonly associated with high blood pressure (BP) and cardiovascular risk, but it is not clear whether BP elevation is primarily associated with increased fat mass or lean mass, which is also increased in obesity. Moreover, few studies have focused on the relationship between haemodynamic determinants of BP, such as stroke volume (SV), cardiac output (CO), and peripheral vascular resistance (PVR), and fat mass or lean mass in healthy men and women.ObjectiveThis study was undertaken to determine whether BP and its haemodynamic determinants were more strongly associated with fat mass or lean mass, and whether the associations differed between males and females.Methods203 healthy human volunteers (103 males, 100 females) aged <50 years were recruited. Body composition was analysed using a Tanita bio‐impedance scale. Clinic (seated) systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured after 5 minutes of rest. Stroke volume and CO were measured using an inert gas re‐breathing method. Peripheral vascular resistance (PVR) was calculated from mean arterial pressure and CO. Data were analysed using Spearman correlation.ResultsIn men, fat mass was positively correlated with DBP (r = 0.51, p < 0.001) only, while lean mass was positively correlated with SBP, CO, and SV (rSBP = 0.33, pSBP < 0.01; rCO = 0.37, pCO < 0.001; rSV = 0.45, pSV < 0.001); lean mass was inversely correlated with PVR (r = −0.31, p < 0.01). In women, fat mass and lean mass were both positively correlated with SBP, DBP, CO and SV (fat mass: rSBP = 0.48, pSBP < 0.001; rDBP = 0.51, pDBP < 0.001; rCO = 0.40, pCO < 0.001; rSV = 0.29, pSV < 0.01) (lean mass: rSBP = 0.41, pSBP < 0.001; rDBP = 0.40, pDBP < 0.001; rCO = 0.52, pCO < 0.001; rSV = 0.47, pSV < 0.01), while lean mass was also inversely correlated with PVR (r = −0.34, p < 0.01).ConclusionsThe relationship between body composition and blood pressure determinants differs between young men and women. These differences should be kept in mind when investigating the physiological mechanisms underlying obesity‐associated hypertension in humans. The impact of lean mass on blood pressure elevation should not be overlooked, particularly in younger males.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sibjotang attenuates Doxorubicin‐Induced Cardiac Hypertrophy: Involvement of necroptosis
Authors: Son Chan Ok , Yoon Jung Joo , Han Byung Hyuk , Kim Hye Yoom , Lee Yun Jung , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Doxorubicin is one for the most widely used anti‐neoplastic agents, however severely limited due to its cumulative cardiotoxicity, which develops over time into congestive heart failure. Sibjotang (Shizaotang), traditional herbal medicine formula, has been reported regulates the body fluid blood pressure homeostasis. The present study was aimed at determining the effect and regulatory mechanism of Sibjotang in doxorubicin‐induced cardiotoxicity in H9c2 cells. Immunofluorescence staining analysis showed that Sibjotang decreased doxorubicin‐induced increase in H9c2 cardiomyocytes size in does dependent manner. Pre‐treatment with Sibjotang significantly inhibited doxorubicin‐induced cardiac hypertrophic markers such as ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and β‐MHC (β‐myosin heavy chain) mRNA expression levels. Sibjotang reduced hypertrophy‐associated transcription factor GATA 4 (GATA binding factor 4) expression. Pre‐treatment with Sibjotang significantly inhibited doxorubicin‐induced necroptosis‐associated kinase such as receptor‐interacting serine/threonine‐protein kinase RIPK1 and RIPK3 without affecting cell viability. In conclusion, doxorubicin‐induced cardiac hypertrophy and necroptosis were attenuated by Sibjotang. Therefore, Sibjotang may be potential herbal therapies targeting cardiotoxicity resulting from anti‐cancer agents.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Beneficial Changes Promoted by L‐arginine and Aliskiren in Resistance Vessels in 2K1C hypertensive rats
Authors: Mengal Vinicius , Tiradentes Renata Viana , Santuzzi Cintia Helena , de Almeida Simone Alves , de Abreu Glaucia Rodrigues , Gouvea Sonia Alves 
Published: June 2021

Renovascular hypertension is characterized by increased angiotensin II and oxidative stress and by endothelial dysfunction. By acting on multiple targets and promoting diverse actions, angiotensin II (Ang II) plays a pivotal role in vascular dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and L‐arginine (L‐arg) would restore endothelial dysfunction and reduce inflammation and oxidative stress in a rat renovascular hypertension model. Hypertension was induced by clipping the right renal artery, and the following five groups were divided: SHAM operated; 2‐kidney, 1‐clip (2K1C); 2K1C plus ALSK; 2K1C plus L‐ARG; and 2K1C plus ALSK+ L‐ARG. The vascular reactivity to norepinephrine (NE; 10(−9) to 2 × 10(−3) mol/L) and acetylcholine (ACh; 10(−10) to 10(−3) mol/L) was evaluated in the mesenteric arteriolar bed through concentration‐effect curves. The structure was assessed by histology and biomolecular analyzes were done via western blot, lipid peroxidation, DHE and DAF. For 4 weeks, blood pressure (BP) was monitored and endothelium‐dependent vasoconstriction and relaxation were assessed in mesenteric arteriolar. ALSK+L‐arg reduced BP and the contractile response to norepinephrine and improved acetylcholine relaxation. Incubation with N‐nitro‐L‐arginine methyl ester (L‐NAME) and L‐NAME+ Indometacin increased the response to norepinephrine in the 2K1C group and the effect was greater and partially improved, respectively, with the treatments. However, It was improved acetylcholine relaxation with the both of the treatments. The bioavailability of nitric oxide increased with the treatments, and the inflammation and oxidative stress was reduced with the treatments. L‐arginine and aliskiren attenuates the morphofunctional deleterious effects of Ang II on resistance vessels. The benefits of L‐arginine and aliskiren seem to occur through restoring the balance of ROS/NO. Therefore, this study opened new avenues for further clinical targeting of the treatment of cardiovascular diseases related to activation of the renin‐angiotensin system. In conclusion, combined ALSK+L‐arg treatment normalizes BP and prevents endothelial dysfunction in 2K1C hypertensive rats.Support or Funding InformationThis research was supported by a CNPq research grants. This study was funded by Fundação de Amparo a Pesquisa do Espirito Santo (FAPES‐Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq‐Brazil).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise Hypertension and Aortic Stiffness in Adults Survivors of Prematurity
Authors: Peters Matthew E 
Published: June 2021

Matthew Peters, Christopher R. Barnard, Emily T. Farrell, Mari Palta, Marlowe W. Eldridge, Harald M. Stauss, John F. Dagle, Jeffrey Segar, Gary L. Pierce, Melissa L. BatesRationaleThe long‐term consequences of premature birth, and the interventions necessary to treat premature birth, are not well understood. Previous studies have shown pulmonary insufficiencies, but few have looked at hemodynamic variables. None have looked into exercise and hypoxia intolerance in these adults who were born prematurely.ObjectivesTo determine exercise capacity and hemodynamic responses during exercise and hypoxia in prematurely born adults. To derive pulse wave velocity under normoxia and hypoxiaMethodsPreterm (N=10) and term‐born, aged matched subjects (N=12), were performed incremental exercise under normoxia (21% O2) or hypoxia (12% O2) until volitional maximum.ResultsPreterm subjects and term‐born subjects have similar forced expiratory volume in one second (FEV1), functional vital capacity (FVC), FEV1/FVC, diffusion capacity of carbon monoxide, maximum wattage, and VO2 max. The preterm adults had higher heart rates, systolic blood pressure, and pulse pressure throughout the exercise protocol under normoxia and hypoxia. They had a higher diastolic pressure and mean arterial pressure during exercise under normoxia, but had lower diastolic blood pressure and mean arterial pressure under hypoxia. Adults born prematurely also had higher pulse wave velocities in normoxia and hypoxia, but there was no effect of the gas condition.ConclusionsThis study demonstrated that heart rate and blood pressure responses to exercise in adults who survived prematurity differ from those who were born at full‐term. Premature adults elevated blood pressure more than term‐born adults when exercise under normoxia. A similar trend is seen under hypoxia, however, diastolic blood pressure falls which may be due to increased sensitivity to or production of vasodilators under hypoxic conditions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
GPR37L1 Regulates the Expression and Function of NHE3 in Renal Proximal Tubule Cells
Authors: Zheng Xiaoxu , Asico Laureano D , Armando Ines , Jose Pedro A , Konkalmatt Prasad R 
Published: June 2021

The orphan G protein‐coupled receptor 37L1 (GPR37L1) has strong homology with the endothelin‐B receptor but it does not interact with endothelin. GPR37L1 is known to be expressed in several regions in the brain, but its expression profile and function in peripheral tissues are poorly understood. We determined the expression profile of GPR37L1 in mouse organs by RT‐PCR and immunoblot analyses and further used immunohistochemical analyses to locate the sites of GPR37L1 expression within the tissues. Quantitative RT‐PCR revealed that the expression of GPR37L1 was highest in the brain, heart, stomach, testis, and ovary and less in the kidney, liver, lung, spleen, pancreas, and skeletal muscle. Immunohistochemical analyses revealed the expression of GPR37L1 in specific regions within some organs, e.g., neurons in the granular layer of the cerebellum, epithelial cells lining the airway of the lung, epithelial cells lining the gastric mucosa, apical membrane of renal proximal tubule cells (RPTCs), early spermatids in seminiferous tubule of the testis, and granulosa cells in the secondary follicle of the ovary. Transient expression of GPR37L1 in human (h)RPTCs increased sodium transport whereas silencing of GPR37L1 decreased sodium transport. Inhibition of sodium hydrogen exchanger type 3 (NHE3) expression abrogated the GPR37L1‐mediated increase in sodium transport. Renal‐restricted silencing of Gpr37l1 in mice increased urine output and sodium excretion and decreased systolic and diastolic blood pressures. The renal‐selective silencing of GPR37L1 decreased the expression of NHE3 but not the expression of Na+/K+‐ATPase or sodium/glucose cotransporter 2. Over‐expression of GPR37L1 in hRPTCs increased the phosphorylation of ERK1/2 (1.73 ± 0.11‐fold, P<0.05) and AKT (1.89 ± 0.12‐fold, P<0.01) and decreased forskolin‐induced cAMP production (38% ± 4.9). Our findings show that in the kidney GPR37L1 increases luminal RPT sodium transport and blood pressure by increasing NHE3 expression, via the ERK1/2 and AKT pathway and increasing NHE3 function by suppressing cAMP production via Gai. Taken together, these results show that GPR37L1 expressed in RPTCs plays an important role in increasing renal sodium transport; GPR37L1 may be a novel target to design drugs to treat hypertension.Support or Funding InformationUS National Institute of Health R56DK116828, R37HL023081, P01HL074940, R01HL092196, R01DK039308, and R01DK090918, and National Kidney Foundation NKF‐MD‐Mini.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Arterial smooth muscle cell PKD2 (TRPP1) channels contribute to angiotensin‐induced vascular remodeling
Authors: Daker Hailey , Reinert Angela , Fernandez‐Pena Carlos , Jaggar Jonathan H , Bulley Simon 
Published: June 2021

Hypertension is associated with structural changes of resistance‐sized arteries, a process referred to as vascular remodeling, resulting in an increase in total peripheral resistance. One stimulus that exerts changes in arterial structure is an elevation in the vasoconstrictor angiotensin II (ang II), which mediates vascular smooth muscle cell growth, consequently resulting in vascular remodeling. Arterial smooth muscle cell PKD2 (TRPP1) channels, a member of the transient receptor potential (TRP) channel superfamily of ion channels, are upregulated in resistance‐sized arteries in ang II‐treated mice when compared to saline‐perfused controls. In addition, ang II‐treated conditional smooth muscle‐specific PKD2 knockout (PKD2sm−/−) mice demonstrate attenuated arterial wall remodeling and reduced blood pressure. An alteration in the expression and function of vascular smooth muscle cell ion channels also contributes to vascular remodeling through the promotion of cell proliferation. Here, we demonstrate that transient receptor potential canonical type 3 (TRPC3) and epidermal growth factor receptor (EGFR) channels, both indicated previously to contribute to ang II‐mediated vascular remodeling, are upregulated in mesenteric arteries isolated from ang II‐treated mice. During hypertension, TRPC3 channel function is also elevated, as demonstrated by application of the TRPC3 channel blocker pyrazole 3 (Pyr3) to pressurized 3rd and 4th order mesenteric arteries. Ang II‐treated PKD2sm−/− mice show reduced TRPC3 and EGFR expression, as well as decreased TRPC3 function when compared to ang II‐treated PKD2fl/fl controls. These data suggest that arterial smooth muscle cell PKD2 channels may contribute to TRPC3‐induced vascular remodeling in resistance‐sized mesenteric arteries.Support or Funding InformationAHA 16SDG27460007This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blood Flow Restriction Exercise Increases the ACE2/ACE Ratio and ACE2 Shedding in CD34+ Cells in Healthy Individuals
Authors: Joshi Shrinidh , Mahoney Sean , Pitts Logan , McCullough Shane , Hackney Kyle , Jarajapu Yagna PR 
Published: June 2021

Adult CD34+ hematopoietic stem/progenitor cells in the systemic circulation are bone marrow‐derived and have the propensity of maintaining cardiovascular health. We have previously shown that activation of the vascular protective axis of renin angiotensin system (RAS), Angiotensin Converting enzyme‐2 (ACE2)/Angiotensin‐(1–7)/Mas receptor axis stimulates vasoreparative functions of CD34+ cells in health and disease. Importantly, in vitro exposure of CD34+ cells to hypoxia enhanced the expressions of ACE2 and Mas, and stimulated ACE2 shedding, but ACE and AT1 receptors, members of the vascular detrimental axis of RAS were not affected. This study tested if acute regional hypoxia recapitulates the in vitro observations in healthy individuals. Blood flow restriction exercise (BFR) was performed in the lower body by applying 80% limb occlusion pressure (LOP). Delphi personalized tourniquet system was used to accomplish the target LOP. Exercise protocol consisted of total four sets (30/15/15/15 repetitions) of movements at 10% of maximal strength. Muscle oxygen saturation was determined by using MOXY muscle oxygen monitor. Peripheral blood was collected two weeks before (control) and 30 min after BFR. CD34+ cells were enumerated by flow cytometry, and ACE and ACE2 activities in plasma, and in cell lysates and cell‐free supernatants were determined. Plasma concentrations of SDF and VEGF were analyzed by ELISA. BFR prescribed at 80% LOP resulted in muscle oxygen levels of 14.1% compared to 50.9% in the resting condition. As predicted, circulating CD34+ cells were increased following BFR (before 356±59.1 and after 835±62.1/mL blood, P<0.001, n=5), which was associated with increased plasma levels of SDF and VEGF (4‐ and 3‐fold, respectively, compared to control (P<0.001, n=5)). ACE2 activity was increased in the whole cell lysates of Lineage‐negative cells resulting in the ACE2/ACE ratio of 11.7±0.5 compared to the baseline ratio of 9.1±0.9 (P<0.05, n=5). Cell supernatants have 3‐fold increase in ACE2/ACE ratio following BFR compared to the baseline levels (P<0.001, n=5). Collectively, these findings provide compelling evidence for the upregulation of ACE2, the vasoprotective enzyme of RAS, by acute regional hypoxia in HSPCs. BFR‐exercise regimen could be a promising approach for enhancing or restoring cardiovascular health in individuals that are poor mobilizers or those at risk for the development of cardiovascular complications.Support or Funding InformationNational Institute of General Medical Sciences (NIGMS) and National Institute of Aging (NIA) AG056881.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.