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    9870 results match your criteria American Journal of Physiology - Heart and Circulatory Physiology[Journal]

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    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Medical Biophysics; MSB 407, University of Western Ontario, Canada.
    The increasing prevalence and severity of clinical depression is strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes, although demonstrating a sexual disparity where females are at lower risk than males for subsequent cardiovascular events. To determine potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in females, we exposed male and female ({plus minus}ovariectomy) rats to the unpredictable chronic mild stress (UCMS) model for 8 weeks and determined depressive symptom severity, vascular reactivity in aortic rings (AR) and ex vivo middle cerebral arteries (MCA), and determined the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, levels in females were significantly worse than in males or OVX. Read More

    The HCM-linked W792R mutation in cardiac myosin binding protein-C reduces C6 FnIII domain stability.
    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Pediatrics, University of Wisconsin-Madison, United States.
    Cardiac myosin binding protein-C (cMyBP-C) is a functional sarcomeric protein that regulates contractility in response to contractile demand, and many mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight into the effects of disease-causing cMyBP-C missense mutations on contractile function, we expressed the pathogenic W792R mutation in mouse cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects using three-dimensional engineered cardiac tissue (mECT) constructs. Based on complete conservation of tryptophan at this location in FnIII domains, we hypothesized that the W792R mutation affects folding of the C6 FnIII-domain, destabilizing the mutant protein. Read More

    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Medical Biophysics; MSB 407, University of Western Ontario, Canada.
    While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and that for depressive symptoms; creating a combined condition of severely elevated cardiovascular disease risk. In this companion manuscript, we determine the impact of pre-existing metabolic disease on the relationship between chronic stress//depressive symptoms and vascular function, using the obese Zucker (OZR) and the unpredictable chronic mild stress UCMS models. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive symptoms on vascular function demonstrated in female lean Zucker rats (LZR). Read More

    Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.
    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Moecular Pahogenesis, Medical Researh Institute, Toko Med. Dent. University, Japan.
    Mutations in genes encoding components of sarcomere cause cardiomyopathy, which is often associated with abnormal Casensitivity of muscle contraction. We previously showed that a heart-specific myosin light chain phosphatase small subunit, hHS-M, increases the Ca-sensitivity of muscle contraction. The aim of this study was to investigate the function of hHS-Min vivo and the causative role of abnormal Casensitivity in cardiomyopathy. Read More

    The impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline.
    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Research Center, Montreal Heart Institute, Canada.
    Aging is a modern concept: human life expectancy has more than doubled in less than 150 years in Western countries. Longer lifespan, however, reveals age-related diseases, including cerebrovascular diseases. The vascular system is a prime target of aging: the "wear and tear" of large elastic arteries exposed to a life-long pulsatile pressure causes arterial stiffening by fragmentation of elastin fibers and replacement by stiffer collagen. Read More

    Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice.
    Am J Physiol Heart Circ Physiol 2018 Feb 16. Epub 2018 Feb 16.
    Medicine, University of California, Los Angeles, United States.
    Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit onset of aortic calcification. Whether teriparatide affects progression of pre-existing aortic calcification, widespread among this patient population, is unknown. Read More

    Atrial Arrhythmias and Autonomic Dysfunction in Rats Exposed to Chronic Intermittent Hypoxia.
    Am J Physiol Heart Circ Physiol 2018 Feb 9. Epub 2018 Feb 9.
    Physiology & Pharmacology and Medicine, Western University, Canada.
    Obstructive sleep apnea (OSA), which involves chronic, intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability, and evaluated the role of autonomics in CIH promotion of AF. Read More

    Coronary Microvascular Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction.
    Am J Physiol Heart Circ Physiol 2018 Feb 9. Epub 2018 Feb 9.
    Medicine/Cardiology, University of Chicago Pritzker School of Medicine, United States.
    Background: There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesize that coronary microvascular dysfunction is common in these patients.

    Methods And Results: In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF (left ventricular (LV) ejection fraction {greater than or equal to} 50% and with clinical HF), were compared to similar patients without HFpEF. Read More

    Upregulated galectin-3 is not a critical disease mediator of cardiomyopathy induced by β-adrenoceptor overexpression.
    Am J Physiol Heart Circ Physiol 2018 Feb 9. Epub 2018 Feb 9.
    Experimental Cardiology, Baker IDI Heart and Diabetes Institute, Australia.
    Pre-clinical studies have demonstrated that anti-galectin-3 (Gal-3) interventions are effective in attenuating cardiac remodeling, fibrosis and dysfunction. We determined, in a transgenic (TG) mouse model of fibrotic cardiomyopathy, whether galectin-3 expression was elevated and whether Gal-3 played a critical role in disease development. We studied mice with fibrotic cardiomyopathy due to cardiac overexpression of human β-adrenoceptor (β-TG). Read More

    Water transport and homeostasis as a major function of erythrocytes.
    Am J Physiol Heart Circ Physiol 2018 Feb 2. Epub 2018 Feb 2.
    Bioengineering, UCSD, United States.
    Erythrocytes have long been known to change volumes and shapes in response to different salt concentrations. Aquaporin-1 (AQP1) was discovered in their membranes more than 20 years ago. The physiological roles of volume changes and AQP1 expression, however, have remained unclear. Read More

    A population neuroscience approach to the study of cerebral small vessel disease in mid- and late-life: an Invited Review.
    Am J Physiol Heart Circ Physiol 2018 Feb 2. Epub 2018 Feb 2.
    Public Health, University of Pittsburgh, United States.
    Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent, but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. Read More

    Maternal High Fat Diet Acts on the Brain to Induce Baroreflex Dysfunction and Sensitization of Angiotensin II-Induced Hypertension in Adult Offspring.
    Am J Physiol Heart Circ Physiol 2018 Jan 26. Epub 2018 Jan 26.
    Department of Psychology, University of Iowa, United States.
    Accumulating evidence indicates that maternal high fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress and proinflammatory cytokines that alter angiotensin II and tumor necrosis factor-α (TNF-α) actions and sensitize the angiotensin II-elicited hypertensive response in adult offspring. All offspring were cross-fostered by dams on the same or opposite diet to yield 4 groups: offspring from normal fat control diet (CD)-fed dams suckled by CD-fed dams (OCC) or by HFD-fed dams (OCH), and offspring from HFD-fed dams fed HFD suckled by CD-fed dams (OHC) or by HFD-fed dams (OHH). Read More

    Actin Polymerization Contributes to Enhanced Pulmonary Vasoconstrictor Reactivity Following Chronic Hypoxia.
    Am J Physiol Heart Circ Physiol 2018 Jan 26. Epub 2018 Jan 26.
    Cell Biology and Physiology, University of New Mexico Health Sciences Center, United States.
    Chronic hypoxia (CH) augments basal and endothelin 1 (ET-1)-induced pulmonary vasoconstrictor reactivity through reactive oxygen species (ROS) generation and RhoA/Rho kinase (ROCK)-dependent myofilament Casensitization. Because ROCK promotes actin polymerization and the actin cytoskeleton regulates smooth muscle tension, we hypothesized that actin polymerization is required for enhanced basal and ET-1-dependent vasoconstriction following CH. To test this hypothesis, both endpoints were monitored in pressurized, endothelium-disrupted pulmonary arteries (4-5order) from control and CH (4 wk at 0. Read More

    Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure.
    Am J Physiol Heart Circ Physiol 2018 Jan 26. Epub 2018 Jan 26.
    Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, United States.
    The imbalance between the synthesis of reactive oxygen species (ROS) and their elimination by antioxidant defense systems, results in macromolecular damage and disruption of cellular redox signaling, affecting cardiac structure and function, thus contributing to contractile dysfunction, myocardial hypertrophy and fibrosisinchronic heart failure (CHF). The Keap1-Nrf2 pathway is an important antioxidant defense mechanism and is closely associated with oxidative stress-mediated cardiac remodeling in CHF. In the current study, we investigated the regulation of myocardial Nrf2 in the post myocardial infarction (MI) state. Read More

    TIMP3 deficiency exacerbates iron-overload mediated cardiomyopathy and liver disease.
    Am J Physiol Heart Circ Physiol 2018 Jan 26. Epub 2018 Jan 26.
    Medicine, University of Alberta, Canada.
    Chronic iron-overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron-overload. We investigated the role of tissue inhibitor of metalloproteinase-3 (TIMP3) in iron-overload mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3) and wildtype (WT) mice to 12 weeks of chronic iron-overload. While iron-overload in the WT group developed diastolic dysfunction, iron-overloaded Timp3mice showed worsened cardiac dysfunction coupled with systolic dysfunction. Read More

    Epithelial Nachannel (ENaC) differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice.
    Am J Physiol Heart Circ Physiol 2018 Jan 26. Epub 2018 Jan 26.
    Department of Physiology, University of Otago, New Zealand.
    A potential "new player" in arteries for mediating shear stress responses is the Epithelial Sodium Channel (ENaC). ENaC's contribution as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance) is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (3rd order mesenteric) arteries isolated from C57Bl/6J mice. Read More

    Sympathetically-mediated cardiac responses to isolated muscle metaboreflex activation following exercise are modulated by body position in humans.
    Am J Physiol Heart Circ Physiol 2017 Dec 15. Epub 2017 Dec 15.
    Faculty of Physical Education, University of Brasilia, Brazil.
    Isolated muscle metaboreflex activation with post-handgrip exercise ischemia (PEI) increases sympathetic nerve activity and partially maintains the exercise-induced increase in blood pressure, but a smaller heart rate (HR) response occurs. The cardiopulmonary baroreceptors, mechanically sensitive receptors that respond to changes in central blood volume and pressure, are strongly associated with changes in body position and upon activation elicit reflex sympathoinhibition. Here, we tested the hypothesis that postural changes modulate the sympathetically-mediated cardiac response to PEI in humans. Read More

    Increased (Pro)renin Receptor Expression in Subfornical Organ Neurons in Hypertensive Humans.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Pharmacology and Physiology & Cell Biology, University of Nevada-Reno, United States.
    The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity, and sodium and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Read More

    Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's disease and vascular cognitive impairment.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Physiology / Barshop Institute, University of Texas HSC, San Antonio, United States.
    An intact blood-brain barrier (BBB) limits entry of pro-inflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer's disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive and no interventions are available for treatment or prevention. Read More

    GABAergic contribution to the muscle mechanoreflex-mediated heart rate responses at the onset of exercise in humans.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Faculty of Physical Education, University of Brasilia, Brazil.
    Previous studies indicated that central GABAergic mechanisms are involved in the heart rate (HR) responses at the onset of exercise. Based on previous research that showed similar increases in HR during passive and active cycling, we reasoned that the GABAergic mechanisms involved in the HR responses at the exercise onset is primarily mediated by muscle mechanoreceptors afferents. Therefore, in this study we sought to determine if central GABA mechanisms are involved in the muscle mechanoreflex-mediated HR responses at the onset of exercise in humans. Read More

    From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    University of Oxford, United Kingdom.
    Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and sub-cellular ionic densities on calcium transient dynamics. Read More

    Telomerase reverse transcriptase protects against Angiotensin II induced microvascular endothelial dysfunction.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Medicine, Medical College of Wisconsin, United States.
    A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and anti-inflammatory effects. Although primarily studied in the larger conduit arteries, excess ROS release and a corresponding loss of NO also occurs in the smaller resistance arteries of the microcirculation, but underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II). Read More

    Emerging Potential Benefits of Modulating NADMetabolism in Cardiovascular Disease.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Division of Cardiovascular Medicine, University of Iowa, United States.
    Nicotinamide adenine dinucleotide (NAD) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NADis required for the activity of multifunctional enzymes including sirtuins and poly(ADP-ribose) polymerases (PARPs) that regulate post-translational modifications, DNA damage responses, and calcium signaling. Recent research indicates that NADparticipates in a multitude of processes dysregulated in cardiovascular diseases. Read More

    Vitamin D and regulation of vascular cell function.
    Am J Physiol Heart Circ Physiol 2017 Dec 22. Epub 2017 Dec 22.
    Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, United States.
    Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for treatment of various types of cancer and chronic diseases. Read More

    Intermediary Metabolism and Fatty Acid Oxidation: Novel Targets of Electron Transport Chain Driven Injury During Ischemia and Reperfusion.
    Am J Physiol Heart Circ Physiol 2017 Dec 29. Epub 2017 Dec 29.
    Medicine, McGuire Department Veterans Affairs, United States.
    Background: Cardiac ischemia-reperfusion (IR) damages the electron transport chain (ETC) causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during IR. Read More

    Maximal strength training-induced improvements in forearm work efficiency are associated with reduced blood flow.
    Am J Physiol Heart Circ Physiol 2017 Dec 29. Epub 2017 Dec 29.
    Circulation and medical imaging, Norvegian University of Science and Technology, Norway.
    Maximal strength training (MST) improves work efficiency. However, since blood flow is greatly dictated by muscle contractions in arms during exercise, and vascular conductance is lower, it has been indicated that arms rely more upon adapting oxygen extraction than legs in response to the enhanced work efficiency. Thus, to investigate if metabolic and vascular responses are arm-specific, we utilized Doppler-ultrasound and a catheter placed in the subclavian vein to measure blood flow and a-vOduring steady state work in seven young males (24{plus minus}3(SD) years) following six-weeks of handgrip MST. Read More

    Exercise training induces eNOS coupling and restores relaxation in coronary arteries of heart failure rats.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Biomedical Sciences Institute, University of Sao Paulo, Brazil.
    Exercise training (ET) has emerged as a non-pharmacological therapy for cardiovascular diseases because of its helpful milieu for improving vascular function. The aim of the present study was to assess whether ET reverses the alterations in vascular reactivity observed in heart failure (HF)-related coronary arteries and to elucidate the molecular mechanisms involved in these adjustments. Male Wistar rats were subjected to either coronary artery ligation or sham operation (SO). Read More

    Macrophage-dependent impairment of α-adrenergic autoreceptor function in sympathetic neurons from DOCA-salt but not high fat diet-induced hypertensive rats.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Neuroscience and Pharmacology & Toxicology, Michigan State University, United States.
    DOCA-salt and obesity-related hypertension are associated with inflammation and sympathetic nervous system hyperactivity. Prejunctional α-adrenergic receptors (αARs) provide negative feedback to norepinephrine release from sympathetic nerves through inhibition of N-type Cachannels. Increased neuronal norepinephrine release in DOCA-salt and obesity-related hypertension occurs through impaired αAR signaling, however, the mechanisms involved are unclear. Read More

    Guidelines for Authors and Reviewers on Antibody Use in Physiology Studies.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Physiology and Biophysics, University of Mississippi Medical Center, United States.
    Antibody use is a critical component of cardiovascular physiology research, and antibodies are used to monitor protein abundance (immunoblotting) and protein expression and localization (in tissue by immunohistochemistry and in cells by immunocytochemistry). With ongoing discussions on how to improve reproducibility and rigor, the goal of this review is to provide best practice guidelines regarding how to optimize antibody use for increased rigor and reproducibility in both immunoblotting and immunohistochemistry approaches. Read More

    Differences in L-type calcium channel activity partially underlie the regional dichotomy in pumping behavior by murine peripheral and visceral lymphatic vessels.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Medical Pharmacology & Physiology, University of Missouri, United States.
    We identified a regional dichotomy in murine lymphatic contractile function with regard to vessel location within either the periphery or visceral cavity. All vessels isolated from peripheral regions; cervical, popliteal, inguinal, axillary, and inter-nodal inguinal axillary (Ing-Ax) developed robust contractions with maximal ejection fractions (EFs) of 50-80% in our ex vivo isobaric myograph experiments. Conversely, vessels isolated from the visceral cavity (mesenteric, TD, and iliac) demonstrated maximal EFs below 15%. Read More

    Important role of endothelium-dependent hyperpolarization in pulmonary microcirculation in male mice -Implications for hypoxia-induced pulmonary hypertension.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan.
    Endothelium-dependent hyperpolarization (EDH) plays important roles in systemic circulation, whereas its role in pulmonary circulation remains largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in pulmonary circulation in general and in PH in particular. Read More

    Guidelines for Measuring Cardiac Physiology in Mice.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Cardiac Ultrasound Laboratory, Hospital of the University of Pennsylvania, United States.
    Cardiovascular disease is a leading cause of death, and translational research is needed to better understand mechanisms whereby the left ventricle responds to injury. Mouse models of heart disease have provided valuable insights into mechanisms that occur during cardiac aging and in response to a variety of pathologies. Assessing cardiovascular physiological responses to injury or insult is an important and necessary component of this research. Read More

    Thrombosis, systemic and cardiac oxidative stress and DNA damage induced by pulmonary exposure to diesel exhaust particles, and the effect of nootkatone thereon.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    Department of Pharmacology, Sultan Qaboos University, College of Medicine and Health Sciences.
    Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particles-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. Read More

    Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation and on cerebral blood flow after a focal ischemic insult in rats.
    Am J Physiol Heart Circ Physiol 2018 Jan 5. Epub 2018 Jan 5.
    SIPBS, University of Strathclyde, Scotland.
    2-Arachidonoylglycerol (2-AG) is a major modulator of blood flow and platelet aggregation and a potential neuroprotectant. The present study investigated the effects of 2-AG on cerebral blood flow (CBF) in the first critical hours during middle cerebral artery occlusion (MCAO) and on platelet aggregation for the first time in rats. Adult male Sprague Dawley rats (n=30) underwent permanent MCAO under isoflurane anaesthesia and were randomly assigned to receive either 2-AG (6 mgkg-1, i. Read More

    Superoxide Inhibition Restores Endothelium-Dependent Dilatation in Aging Arteries by Enhancing Impaired Adherens Junctions.
    Am J Physiol Heart Circ Physiol 2018 Jan 12. Epub 2018 Jan 12.
    Anesthesiology and Critical Care Medicine, Johns Hopkins University, United States.
    Endothelium-dependent, nitric oxide (NO)-mediated dilatation is impaired in aging arteries. The dysfunction reflects increased production of reactive oxygen species (ROS), is reversed by inhibiting superoxide with superoxide dismutase (SOD) mimics, and is assumed to reflect superoxide-mediated inactivation of NO. However, the dysfunction also reflects Src-dependent degradation and loss of VE-cadherin from adherens junctions, resulting in a selective impairment in the ability of the junctions to amplify endothelial dilatation. Read More

    Am J Physiol Heart Circ Physiol 2018 Jan 12. Epub 2018 Jan 12.
    Research Division, Ochsner Clinic Foundation, United States.
    It has become clear that the vasoactive peptide angiotensin II, like other so-called intracrines, can act in the intracellular space. Evidence has accumulated indicating that such angiotensin II activity can be upregulated in disease states and cause pathology. Indeed, other intracrines appear to be involved in disease pathogenesis as well. Read More

    Guidelines for Experimental Models of Myocardial Ischemia and Infarction.
    Am J Physiol Heart Circ Physiol 2018 Jan 12. Epub 2018 Jan 12.
    Institut fur Pathophysiologie, Universitatsklinikum Essen, Germany.
    Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angina to hibernation to permanent occlusion, and while reperfusion is mandatory for salvage from ischemic injury, reperfusion also inflicts injury on its own. In this consensus statement, we present recommendations for animal models of myocardial ischemia and infarction. Read More

    Cardiac Vanilloid Receptor-1 Afferent Depletion Enhances Stellate Ganglion Neuronal Activity and Efferent Sympathetic Response to Cardiac Stress.
    Am J Physiol Heart Circ Physiol 2018 Jan 16. Epub 2018 Jan 16.
    Cardiac Arrhythmias Center, UCLA, United States.
    Afferent fibers expressing the vanilloid receptor 1 (VR1) channel are implicated in cardiac nociception, however, their role in modulating reflex responses to cardiac stress is not well-understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals (ARIs), and in vivo activity of stellate ganglion (SG) neurons (SGNs) were recorded in control and RTX-treated animals. Read More

    Sex Differences in Abdominal Aortic Aneurysms.
    Am J Physiol Heart Circ Physiol 2018 Jan 19. Epub 2018 Jan 19.
    Pharmacology, Tulane University School of Medicine, United States.
    Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Read More

    Overexpression of the Neuronal Human (Pro)renin Receptor Mediates Angiotensin II-Independent Blood Pressure Regulation in the Central Nervous System.
    Am J Physiol Heart Circ Physiol 2017 Dec 15. Epub 2017 Dec 15.
    Pharmacology and Physiology & Cell Biology, University of Nevada-Reno, United States.
    Despite advances in anti-hypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system (RAS) that mediates angiotensin II (Ang II) formation in the CNS. Although the PRR also mediates Ang II-independent signaling, the importance of these pathways in BP regulation is unknown. Read More

    Ferroptosis: Beating on Death's Door.
    Am J Physiol Heart Circ Physiol 2017 Dec 6. Epub 2017 Dec 6.
    Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Canada.
    One of the most fascinating concepts to impact contemporary biology to date is the idea that cell death is a highly regulated and programmed event. Cardiac cells can die by apoptosis or necrosis and in some instances by autophagy. Ferroptosis, is a new form of regulated cell death that is gaining considerable attention, that links de-regulated iron metabolism with peroxidative lipid injury. Read More

    PACAP(6-38) or kynurenate microinjections into the RVLM prevent development of sympathetic long-term facilitation following acute intermittent hypoxia.
    Am J Physiol Heart Circ Physiol 2017 Dec 6. Epub 2017 Dec 6.
    High Blood Pressure Group, Heart Research Institute, University of Sydney, Australia.
    Background And Purpose: Intermittent hypoxia causes a persistent increase in sympathetic activity, which progresses to hypertension in chronic conditions such as obstructive sleep apnea (OSA). Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neurotransmitter that causes long-lasting sympathetic excitation. We aimed to determine if intermittent activation of the rostral ventrolateral medulla (RVLM) causes PACAP-mediated elevation of sympathetic nerve activity (sSNA), termed sympathetic long-term facilitation (sLTF). Read More

    Differential effects of alcohol and its metabolite acetaldehyde on vascular smooth muscle cell Notch signaling and growth.
    Am J Physiol Heart Circ Physiol 2018 Jan 8;314(1):H131-H137. Epub 2017 Dec 8.
    Department of Surgery, University of Rochester Medical Center , Rochester, New York.
    Alcohol (EtOH) consumption can variously affect cardiovascular disease. Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth, which are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMCs) were treated with EtOH (25 mM) or ACT (10 or 25 μM). Read More

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