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    9754 results match your criteria American Journal of Physiology - Heart and Circulatory Physiology[Journal]

    1 OF 196

    Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health.
    Am J Physiol Heart Circ Physiol 2017 Sep 15:ajpheart.00500.2017. Epub 2017 Sep 15.
    Massachusetts General Hospital, Boston, MA
    Objective: Exercise improves cardiometabolic and vascular function, though mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. Approach and Results: We performed plasma small RNA sequencing (RNA-seq) in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. Read More

    Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human heart.
    Am J Physiol Heart Circ Physiol 2017 Sep 15:ajpheart.00350.2017. Epub 2017 Sep 15.
    University Medical School.
    Using transgenic mice (TG) that overexpress the human 5-HT4a-receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor, 5-hydroxy-tryptophan (5-HTP), can exert inotropic and chronotropic effects in cardiac preparations from TG but not from wild type (WT): similar results were found in human atrial preparations, as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as wells as in human atria. Read More

    Effect of increases in cardiac contractility on cerebral blood flow in humans.
    Am J Physiol Heart Circ Physiol 2017 Sep 15:ajpheart.00287.2017. Epub 2017 Sep 15.
    Texas Health Presbyterian Hospital Dallas.
    The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine (first a low dose; 5 μg/kg/min and then a high dose; 15 μg/kg/min) for 12 min each. Read More

    Electrophysiological heterogeneity of pacemaker cells in rabbit intercaval region, including SA node: insights from recording multiple ion currents in each cell.
    Am J Physiol Heart Circ Physiol 2017 Sep 15:ajpheart.00253.2016. Epub 2017 Sep 15.
    National Institute on Aging
    Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear, yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPC) sampled from the para-cristal, inter-caval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. Read More

    Rapid estrogen receptor alpha signaling mediated by ERK activation regulates vascular tone in male and ovary-intact female mice.
    Am J Physiol Heart Circ Physiol 2017 Sep 8:ajpheart.00841.2016. Epub 2017 Sep 8.
    Tulane University School of Medicine
    Estrogen has been shown to affect vascular reactivity. Here, we assessed estrogen receptor-alpha (ERα) dependency of estrogenic effects on vasorelaxation via a rapid nongenomic pathway in both male and ovary-intact female mice. We compared the effect of a primary estrogen, 17 beta-estradiol (E2) or 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) (selective ERα agonist). Read More

    The cerebro-cardiovascular response to periodic squat-stand maneuvers in healthy subjects: a time-domain analysis.
    Am J Physiol Heart Circ Physiol 2017 Sep 8:ajpheart.00331.2017. Epub 2017 Sep 8.
    University of Leicester.
    Background: Squat-stand maneuvers (SSMs) have been used to improve the coherence of transfer function analysis (TFA) estimates during the assessment of dynamic cerebral autoregulation (dCA). There is a need to understand the influence of peripheral changes resulting from SSMs on cerebral blood flow, which might confound estimates of dCA.

    Methods: 29 healthy subjects underwent recordings at rest (5 min standing) and 15 SSMs (0. Read More

    Shock and Lethality with Anthrax Edema Toxin in Rats are Associated with Reduced Arterial Responsiveness to Phenylephrine and are Reversed with Adefovir.
    Am J Physiol Heart Circ Physiol 2017 Sep 8:ajpheart.00285.2017. Epub 2017 Sep 8.
    National Institutes of Health
    Introduction: Although edema (ETx) and lethal toxin (LTx) contribute to B. anthracis shock and lethality, mechanisms underlying their cardiovascular effects are unclear. We previously showed that ETx but not LTx inhibited phenylephrine stimulated contraction of aortic rings prepared from healthy rats and adefovir, a selective inhibitor of ETx cAMP production, blocked this effect. Read More

    Age and strain related aberrant Ca(2+) release is associated with sudden cardiac death in the ACTC E99K mouse model of hypertrophic cardiomyopathy.
    Am J Physiol Heart Circ Physiol 2017 Sep 8:ajpheart.00244.2017. Epub 2017 Sep 8.
    Imperial College
    Patients with hypertrophic cardiomyopathy (HCM), particularly young adults, can die from arrhythmia but the mechanism underlying abnormal rhythm formation remains unknown. C57Bl6 x CBA/Ca mice carrying a cardiac actin (ACTC) E99K (Glu99Lys) mutation reproduce many aspects of human HCM including increased myofilament Ca(2+) sensitivity and sudden death in a proportion (up to 40%) of young (28-40 day old) animals. We studied the hearts of transgenic (TG - ACTC E99K) mice and their non-transgenic (NTG) littermates when they were in their vulnerable period (28-40 days old) and when they were adult (8-12 weeks old). Read More

    Carotid Artery Stenosis In Hypertensive Rats Impairs Dilatory Pathways In Parenchymal Arterioles.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00638.2016. Epub 2017 Aug 25.
    Michigan State University.
    Hypertension is a leading risk factor for vascular cognitive impairment and is strongly associated with carotid artery stenosis. In normotensive rats, chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS) leads to cognitive impairment that is associated with impaired endothelium-dependent dilation in parenchymal arterioles (PAs). The aim of this study was to assess the effects of BCAS on PA function and structure in stroke prone spontaneously hypertensive rats (SHRSP), a model of human essential hypertension. Read More

    Age-related impairment of metabo-vascular coupling during cortical spreading depolarization.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00514.2017. Epub 2017 Aug 25.
    University of Texas HSC, San Antonio
    Cortical spreading depolarizations (SDs) may lead to long-lasting alterations in cerebral blood flow (CBF), which contribute to neuronal dysfunction and hypoxic tissue injury. There is growing evidence to suggest that age-related structural and functional alterations of the neurovascular unit significantly increase both the incidence of SDs and aggravate their functional consequences. Recent studies suggest that metabolic signaling plays a major role in modulating cerebral blood flow responses evoked by SDs and provide critical evidence that aging considerably weakens metabovascular coupling with SD. Read More

    HYPERTROPHIC CARDIOMYOPATHY MUTATION IN CARDIAC TROPONIN T (R95H) ATTENUATES LENGTH-DEPENDENT ACTIVATION IN GUINEA PIG CARDIAC MUSCLE FIBERS.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00369.2017. Epub 2017 Aug 25.
    Washington State University
    The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated crossbridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect crossbridge recruitment dynamics to alter myofilament Ca(2+) sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if the hypertrophic cardiomyopathy-linked mutaton (TnTR94H)-induced effects on contractile function would be differently modulated by sarcomere length (SL). Read More

    PLASTICS AND CARDIOVASCULAR HEALTH: PHTHALATES MAY DISRUPT HEART RATE VARIABILITY AND CARDIOVASCULAR REACTIVITY.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00364.2017. Epub 2017 Aug 25.
    Children's National Health System
    Background: Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products, and that these chemicals are bioactive. Recent epidemiological and research studies suggest that phthalate exposure adversely affects cardiovascular function. Read More

    Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00209.2017. Epub 2017 Aug 25.
    Cincinnati Children's Medical Center
    During postnatal heart valve development, glycosaminoglycan (GAG)-rich valve primordia transform into stratified valve leaflets composed of GAGs, fibrillar collagen, and elastin layers accompanied by decreased cell proliferation, as well as thinning and elongation. The neonatal period is characterized by the transition from a uterine environment to atmospheric oxygen, but the role of changing O2 levels in valve extracellular matrix (ECM) composition or morphogenesis are not well-characterized. Here, we show that tissue hypoxia decreases in mouse aortic valves in the days after birth, concomitant with ECM remodeling and cell cycle arrest of valve interstitial cells (VICs). Read More

    Ca(2+)/calmodulin kinase II-dependent regulation of atrial myocyte late Na+ current, Ca(2+) cycling and excitability: a mathematical modeling study.
    Am J Physiol Heart Circ Physiol 2017 Aug 25:ajpheart.00185.2017. Epub 2017 Aug 25.
    The Ohio State University
    Atrial fibrillation (AF) affects more than 3 million people per year in the U.S., and is associated with high morbidity and mortality. Read More

    Preconditioning with the BKCa Channel Activator NS-1619 Prevents Ischemia/Reperfusion-Induced Inflammation and Mucosal Barrier Dysfunction: ROS and HO-1.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00620.2016. Epub 2017 Aug 19.
    University of Missouri School of Medicine
    Activation of large conductance, calcium-activated potassium (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 hours later. The goal of the current study was to determine the role of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild type (WT) or HO-1 null (HO-1(-/-)) mice that were pretreated with NS-1619 or saline vehicle 24 hrs earlier. Read More

    Temporal Dynamics of Cardiac Hypertrophic Growth in Response to Pressure Overload.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00284.2017. Epub 2017 Aug 19.
    UT Southwestern Medical Center
    Hypertension is one of the most important risk factors of heart failure. In response to high blood pressure, the left ventricle manifests hypertrophic growth to ameliorate wall stress, which may progress into decompensation and trigger pathological cardiac remodeling. Despite the clinical importance, the temporal dynamics of pathological cardiac growth remains elusive. Read More

    Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in heart, skin and lung.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00206.2017. Epub 2017 Aug 19.
    University Antwerpen
    The neuregulin-1 (NRG-1)/ErbB system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies indicate that NRG-1 has anti-fibrotic effects in the left ventricle (LV), which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. Read More

    Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal toll-like receptors in rats.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00205.2017. Epub 2017 Aug 19.
    Sapporo Medical University School of Medicine
    Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined roles of renal toll-like receptors (TLRs) in the impact of DM on AKI after MI. Read More

    Moderate-to-Severe Obstructive Sleep Apnea Is Associated with Telomere Lengthening.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00197.2017. Epub 2017 Aug 19.
    Mayo Clinic
    Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. Read More

    α1A-Subtype Adrenergic Agonist Therapy for Failing Right Ventricle.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00153.2017. Epub 2017 Aug 19.
    VA Medical Center, Univ. Calif. San Francisco.
    Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies show that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of LV failure. Read More

    Glucose transporter 4 (GLUT4) deficient hearts develop maladaptive hypertrophy in response to physiologic or pathologic stresses.
    Am J Physiol Heart Circ Physiol 2017 Aug 19:ajpheart.00101.2017. Epub 2017 Aug 19.
    University of Alabama at Birmingham.
    Pathological cardiac hypertrophy may be associated with reduced expression of the GLUT4 glucose transporter in contrast to exercise-induced cardiac hypertrophy, where GLUT4 levels are increased. However, mice with cardiac specific deletion of GLUT4 (G4H-/-) have normal cardiac function in the unstressed state. This study tested the hypothesis that cardiac GLUT4 is required for myocardial adaptations to hemodynamic demands. Read More

    An Update on Hormone Therapy in Postmenopausal Women: Mini-Review for the Basic Scientist.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00383.2017. Epub 2017 Aug 11.
    Kronos Longevity Research Institute.
    The worlds of observational, clinical and basic science collided in 2002 with the publication of results of the Women's Health Initiative (WHI), a large scale, prospective, blinded, randomized-controlled trial designed to provide evidence regarding use of hormone treatment to prevent cardiovascular disease in menopausal women. The results of the WHI dramatically changed clinical practice, negatively impacted funding for hormone research and left scientists to unravel the "why" of the results. Now over a decade and a half since the initial publication of the WHI results, basic and clinical scientists often do not interpret the results of the WHI with the precision needed to move the science forward. Read More

    Exercise of obese mice induces cardioprotection and oxygen-sparing in hearts exposed to high fat-load.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00382.2017. Epub 2017 Aug 11.
    University of Tromsoe - The Arctic University of Norway
    Exercise training is a potent, therapeutic approach in obesity and diabetes that exerts protective effects against development of diabetic cardiomyopathy and ischemic-injury. Acute increases in circulating fatty acids (FAs) during an ischemic insult can challenge the heart, as high FA-load is considered to have adverse cardiac effects. In the present study, we tested the hypothesis that exercise-induced cardiac effects in diet-induced obese mice are abrogated by an acute high FA-load. Read More

    Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00282.2017. Epub 2017 Aug 11.
    University of Iowa.
    We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated eNOS at serine 1177 (P-eNOS(ser1177)), the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young males (25±1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of max over a 2-hr period. Each bout of exercise was separated by 3 min of rest. Read More

    Dietary Modulation of Oxylipins in Cardiovascular Disease and Aging.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00201.2017. Epub 2017 Aug 11.
    University of Manitoba
    Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone and coagulation. As a result, oxylipins are implicated in many conditions characterized by these processes including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. Read More

    Vascular Niche Contribution to Age Associated Neural Stem Cell Dysfunction.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00154.2017. Epub 2017 Aug 11.
    UT Health San Antonio
    Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone (V-SVZ), where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. Read More

    Role of Pattern Recognition Receptors of the Neurovascular Unit in Inflamm-Aging.
    Am J Physiol Heart Circ Physiol 2017 Aug 11:ajpheart.00106.2017. Epub 2017 Aug 11.
    Biological Research Centre, Hungarian Academy of Sciences.
    Aging is associated with chronic inflammation (inflamm-aging) partly mediated by increased levels of damage-associated molecular patterns (DAMPs) which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, like Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are not only expressed in cells of the innate immune system, but other cells as well, including cells of the neurovascular unit (NVU) and cerebral vasculature forming the blood-brain barrier (BBB). Read More

    Modulation of Mesenteric Collecting Lymphatic Contractions by Sigma-1 Receptor Activation and Nitric Oxide Production.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00702.2016. Epub 2017 Aug 4.
    University of South Florida
    Recently it was reported that a sigma receptor antagonist could reduce inflammation-induced edema. Lymphatic vessels play an essential role in removing excess interstitial fluid. We tested the hypothesis that activation of sigma receptors would reduce or weaken collecting lymphatic contractions. Read More

    Temporal changes in the exercise pressor reflex in type 1 diabetic rats.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00399.2017. Epub 2017 Aug 4.
    University of Texas at Austin
    Previous studies have shown that diabetic peripheral neuropathy affects both unmyelinated and myelinated afferents, similar to those evoking the exercise pressor reflex. However, the effect of type 1 diabetes (T1DM) on this reflex is not known. We examined, in decerebrate, male and female T1DM rats (STZ) and healthy controls (CTL), pressor and cardioaccelerator responses to isometric contraction of the hindlimb muscles, during the early and late stages of the disease. Read More

    Anomalous baroreflex functionality inherent in floxed and Cre-Lox mice: An overlooked physiological phenotype.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00346.2017. Epub 2017 Aug 4.
    Chang Gung Memorial Hospital
    The last two decades saw the emergence of Cre-Lox recombination as one of the most powerful and versatile technologies for cell-specific genetic engineering of mammalian cells. Understandably, the primary concerns in the practice of Cre-Lox recombination are whether the predicted genome has been correctly modified, and the targeted phenotypes expressed. Rarely are the physiological conditions of the animals routinely examined because the general assumption is that they are normal. Read More

    Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia/reperfusion without and with ischemic conditioning.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00293.2017. Epub 2017 Aug 4.
    Universitatsklinikum Essen
    Ventricular fibrillation (VF) occurs frequently during myocardial ischemia/reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no-reflow (NR), without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min coronary occlusion/reperfusion. Read More

    Temperature-Dependent Modulation of Regional Lymphatic Contraction Frequency and Flow.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00267.2017. Epub 2017 Aug 4.
    University of Insubria
    Lymph drainage and propulsion are sustained by an extrinsic mechanism, based upon mechanical forces acting from the surrounding tissues against the wall of lymphatic vessels, and by an intrinsic mechanism due to active spontaneous contractions of the lymphatic vessel muscle. Despite heterogeneous, the mechanisms underlying the generation of spontaneous contractions share a common biochemical nature and are thus modulated by temperature. In this study, we challenged excised tissues from rat diaphragm and hind paw, endowed with spontaneously contracting lymphatic vessels, to temperatures from 24 °C (hind paw) or 33 °C (diaphragmatic vessels) to 40 °C while measuring lymphatic contraction frequency (fc) and amplitude. Read More

    The effect of ovariectomy on intracellular calcium (Ca(2+)) regulation in guinea pig cardiomyocytes.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00249.2017. Epub 2017 Aug 4.
    Imperial College
    This study addressed the hypothesis that long-term deficiency of ovarian hormones alters cellular calcium (Ca(2+)) handling mechanisms in the heart resulting in the formation of a pro-arrhythmic substrate. It also tested if estrogen supplementation to ovariectomised guinea pigs reverses any alterations to cardiac Ca(2+) handling and rescues pro-arrhythmic behaviour. Ovariectomy (OVx) or sham operations were performed on female guinea pigs using appropriate anaesthetic and analgesic regimes. Read More

    Primed Polymorphonuclear Leukocytes (PMNLs) from Hemodialysis Patients Enhance Monocyte Transendothelial Migration.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00122.2017. Epub 2017 Aug 4.
    Western Galilee Hospital
    Increased counts and priming of peripheral polymorphonuclear leukocytes (PMNLs) are associated with future or ongoing atherosclerosis, however, the role of PMNLs in enhancing monocytes transendothelial migration is still unclear. Our aims were to examine endothelial and monocytes activation, transmigration and post-transmigration activation, induced ex-vivo by in-vivo primed PMNLs, and the effect of antioxidants on the activation. A unique ex-vivo co-culture system of 3-cells-type was developed in this study, enabling interactions among: primary endothelial cells (HUVEC), monocytes (THP-1, cell line) and in-vivo primed PMNLs from hemodialysis (HD) patients and Healthy Controls (HC). Read More

    The relationship between lymphangion chain length and maximum pressure generation established through in vivo imaging and computational modeling.
    Am J Physiol Heart Circ Physiol 2017 Aug 4:ajpheart.00003.2017. Epub 2017 Aug 4.
    Georgia Institute of Technology
    The intrinsic contraction of collecting lymphatic vessels serves as a pumping system to propel lymph against hydrostatic pressure gradients as it returns interstitial fluid to the venous circulation. We propose and validate that the maximum opposing outflow pressure along a chain of lymphangions at which flow can be achieved increases with the length of chain. Using minimally invasive near-infrared imaging to measure the effective pumping pressure at various locations in the rat tail, we demonstrate increases in the pumping pressure along the length of the tail. Read More

    Visualisation of three pathways for macromolecule transport across cultured endothelium and their modification by flow.
    Am J Physiol Heart Circ Physiol 2017 Jul 28:ajpheart.00218.2017. Epub 2017 Jul 28.
    Imperial College London
    Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger arterial disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. Here we visualised pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Read More

    Intracoronary Delivery of Recombinant TIMP-3 Following Myocardial Infarction: Effects on Myocardial Remodeling and Function.
    Am J Physiol Heart Circ Physiol 2017 Jul 28:ajpheart.00114.2017. Epub 2017 Jul 28.
    University of South Carolina School of Medicine and WJB Dorn VA
    Background And Significance: Ischemia-reperfusion and myocardial infarction causes adverse LV remodeling and heart failure, facilitated by an imbalance in matrix metalloproteinase activation and the endogenous tissue inhibitors of MMPs. We identified that myocardial injections of a recombinant TIMP-3 (human full length) can interrupt post-MI remodeling. However, to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Read More

    CHRONIC HYPERTENSION INCREASES AORTIC ENDOTHELIAL HYDRAULIC CONDUCTIVITY BY UPREGULATING ENDOTHELIAL AQUAPORIN-1 EXPRES-SION.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00651.2016. Epub 2017 Jul 21.
    The City College of New York
    Numerous studies examine aquaporins' role in osmotic water transport in various systems but virtually none focus on aquaporins' role in hydrostatically-driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here we inves-tigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat mod-els of hypertension, the spontaneously hypertensive genetically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohisto¬chemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. Read More

    Prolonged sitting leg vasculopathy: contributing factors and clinical implications.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00326.2017. Epub 2017 Jul 21.
    University of Texas at Arlington.
    Atherosclerotic peripheral artery disease primarily manifests in the medium-to large-sized conduit arteries of the lower extremities. However, the factors underlying this increased vulnerability of leg macrovasculature to disease are largely unidentified. On the basis of recent studies, we propose that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress causes endothelial cell dysfunction, a key predisposing factor to peripheral artery disease. Read More

    Muscle sympathetic nerve activity and volume regulating factors in healthy pregnant and non-pregnant women.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00312.2017. Epub 2017 Jul 21.
    University of Alberta
    Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In non-pregnant humans, volume regulatory factors including plasma osmolality, vasopressin and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume regulating factors, including plasma osmolality, plasma renin activity and arginine vasopressin (AVP). Read More

    Mitochondrial Function in Engineered Cardiac Tissues is Co-Regulated by Extracellular Matrix Elasticity and Tissue Alignment.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00290.2017. Epub 2017 Jul 21.
    University of Southern California
    Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Read More

    Pathophysiology of cardiorenal syndrome in patients with heart failure: Potential therapeutic targets.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00215.2017. Epub 2017 Jul 21.
    National Cerebral and Cardiovascular Center.
    Despite the development of pharmacological inventions and new non-pharamacological techniques to prevent and treat HF, the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Read More

    Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00155.2017. Epub 2017 Jul 21.
    University of Texas Southwestern Medical Center
    Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MR) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Read More

    How Does Pressure Overload Cause Cardiac Hypertrophy and Dysfunction? High Ouabain Affinity Cardiac Na(+) Pumps are Crucial.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00131.2017. Epub 2017 Jul 21.
    University of Maryland Medical School
    Left ventricular hypertrophy is frequently observed in hypertensive patients, and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically-engineered Na(+) pumps, however, demonstrate that cardiac ouabain-sensitive α2 Na(+) pumps play a key role in the pathogenesis of trans-aortic constriction (TAC)-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α2 Na(+) pumps and in mice with cardiac-selective knockout (KO) or transgenic overexpression (TG) of α2 Na(+) pumps. Read More

    Enhanced NO-Dependent Pulmonary Vasodilation Limits Increased Vasoconstrictor Sensitivity in Neonatal Chronic Hypoxia.
    Am J Physiol Heart Circ Physiol 2017 Jul 21:ajpheart.00123.2017. Epub 2017 Jul 21.
    University of New Mexico Health Sciences Center
    Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension (pHTN). However, whether this response to CH results from pulmonary endothelial dysfunction and reduced NO-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. Read More

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