A5007096980- Nitric Oxide and Endothelin Effects
- Cardiovascular Health and Disease Prevention
- Receptor Mechanisms and Signaling
- Cardiac, Anesthesia and Surgical Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adipose Tissue and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Renin-Angiotensin System Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Blood properties and coagulation
- Spaceflight effects on biology
- Regulation of Appetite and Obesity
- Pulmonary Hypertension Research and Treatments
- High Altitude and Hypoxia
- Heart Rate Variability and Autonomic Control
- Cardiac Ischemia and Reperfusion
- Hemodynamic Monitoring and Therapy
- Cardiac electrophysiology and arrhythmias
- Histone Deacetylase Inhibitors Research
- Blood transfusion and management
- Sulfur Compounds in Biology
- Blood Pressure and Hypertension Studies
- Biochemical Analysis and Sensing Techniques
- Erythrocyte Function and Pathophysiology
- Pregnancy and preeclampsia studies
University of Alabama at Birmingham
2019-2025
The University of Texas at Austin
2024
University of Alabama
2024
Johns Hopkins University
2013-2023
Johns Hopkins Medicine
2013-2023
Walter de Gruyter (Germany)
2018-2023
Advisory Board Company (United States)
2018-2023
University of Würzburg
2014-2023
University of Padua
2021
National Agricultural Library
2018-2020
Rationale: Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization is termed hyperpolarizing (EDHF). Hydrogen sulfide (H 2 S) a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. Objective: The purpose this...
Background— Although abnormal l -arginine NO signaling contributes to endothelial dysfunction in the aging cardiovascular system, biochemical mechanisms remain controversial. -arginine, synthase (NOS) precursor, is also a substrate for arginase. We tested hypotheses that arginase reciprocally regulates NOS by modulating bioavailability and upregulated vasculature, contributing depressed function. Methods Results— Inhibition of with (S)-(2-boronoethyl)- -cysteine, HCl (BEC) produced...
Human obesity leads to an increase in respiratory demands. As becomes more pronounced some individuals are unable compensate, leading elevated arterial carbon dioxide levels (PaCO2 ), alveolar hypoventilation, and increased cardiorespiratory morbidity mortality (Pickwickian syndrome). The mechanisms that link hypoventilation unknown, but thought involve depression of central control mechanisms. Here we report obese C57BL/6J-Lep ob mice, which lack circulating leptin, also exhibit PaCO2 ( >...
Short chain fatty acid (SCFA) metabolites are byproducts of gut microbial metabolism that known to affect host physiology via G protein-coupled receptor (GPCRs). We previously showed an acute SCFA bolus decreases blood pressure (BP) in anesthetized mice, effect mediated primarily Gpr41. In this study, our aims were identify the cellular localization Gpr41 and determine its role BP regulation. localized vascular endothelium using RT-PCR: is detected intact vessels (with endothelium) but...
Whether left ventricular hypertrophy (LVH) in obesity results from increased hemodynamic load or altered neurohormonal signaling remains controversial. Dysregulation of leptin, a neurohormone essential to energy homeostasis, is implicated the pathogenesis obesity. Because leptin has cardiovascular bioactivity, we hypothesized that disruption mediates development obesity-associated LVH.We measured (LV) wall thickness and LV mass with echocardiography mice lacking (ob/ob, n=15) functional...
alpha(1)-adrenergic receptors (alpha(1)ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (alpha(1a), alpha(1b), alpha(1 d)) mediating these effects is unknown varies with species studied. In order to understand mechanisms underlying cardiovascular responses acute stress chronic catecholamine exposure (as seen aging), we tested two hypotheses: (1) human alpha(1)AR expression differs bed, (2) age influences expression.Five hundred vessels...
There is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate leads nitric oxide synthase (eNOS) uncoupling and vivo chronic inhibition restores nitroso-redox balance, improves function, increases vascular compliance old rats. Arginase activity rats was significantly increased compared with shown young Old had lower (NO) higher superoxide (O2(-)) production than young. Acute both NOS, N(G)-nitro-l-arginine...
Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic cells. Here, we demonstrate that vascular is increased atherogenic-prone apolipoprotein E–null (ApoE −/− ) wild-type mice fed a high cholesterol diet. In ApoE mice, selective II inhibition or deletion of the gene (Arg mice) prevents high-cholesterol diet–dependent decreases production, reactive oxygen species restores function, oxidized lipoprotein–dependent increases...
Although interactions between superoxide ( \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{O}}_{2}^{{\cdot}-}\end{equation*}\end{document} ) and nitric oxide underlie many physiologic pathophysiologic processes, regulation of this crosstalk at the enzymatic level is poorly understood. Here, we demonstrate...
Aging leads to a multitude of changes in the cardiovascular system, including systolic hypertension, increased central vascular stiffness, and pulse pressure. In this paper we will review effects age-associated stiffness on blood pressure, augmentation index, cardiac workload. Additionally describe wave velocity as method measure impact an index health predictor adverse outcomes. Furthermore, discuss underlying mechanisms how these may be modified order change A thorough understanding...
Arginase, expressed in endothelial cells and upregulated aging blood vessels, competes with NO synthase (NOS) for l -arginine, thus modulating vasoreactivity attenuating signaling. Moreover, arginase inhibition restores NOS signaling -arginine responsiveness old rat aorta. The isoform responsible NOS, however, remains unknown. Because isoform-specific inhibitors are unavailable, we used an antisense (AS) oligonucleotide approach to knockdown I (Arg I). Western blot quantitative PCR confirmed...
Disruption of leptin signaling is associated with obesity, heart failure, and cardiac hypertrophy, but the role in myocyte apoptosis unknown. We tested hypothesis that increases leptin-deficient ob/ob leptin-resistant db/db mice aging left ventricular increased DNA damage, decreased survival. studied young (2- to 3-month-old) old (12- 14-month-old) wild-type (WT) controls (n=2 4 per group). As expected, wall thickness weights were similar among , WT mice, higher versus WT. Young showed...
Endothelial function is impaired in aging because of a decrease NO bioavailability. This may be, part, attributable to increased arginase activity, which reciprocally regulates synthase (NOS) by competing for the common substrate, L-arginine. However, high Km (>1 mmol/L) compared with NOS (2 20 micromol/L) seemingly makes direct competition substrate unlikely. One mechanisms exerts its effects posttranslational modification through S-nitrosylation protein cysteines. We tested hypothesis that...
Oxidized low-density lipoprotein (OxLDL) impairs NO signaling and endothelial function, contributes to the pathogenesis of atherosclerosis. Arginase reciprocally regulates levels in cells by competing with synthase for substrate l-arginine. In human aortic cells, OxLDL stimulation increased arginase enzyme activity a time- dose-dependent manner. reached its maximum as early 5 minutes, was maintained period more than 48 hours, associated reciprocal decrease metabolite (NOx [nitrite nitrate])...
Rationale : Although an age-related decrease in NO bioavailability contributes to vascular stiffness, the underlying molecular mechanisms remain incompletely understood. We hypothesize that constrains activity of matrix crosslinking enzyme tissue transglutaminase (TG2) via S -nitrosylation young vessels, a process is reversed aging. Objective sought determine whether endothelium-dependent regulates TG2 by and this stiffness. Methods Results first demonstrate suppresses increases cellular...
Erythrocyte cell membranes undergo morphologic changes during storage, but it is unclear whether these are reversible. We assessed erythrocyte membrane deformability in patients before and after transfusion to determine the effects of storage duration reversible transfusion.Sixteen undergoing posterior spinal fusion surgery were studied. was compared between those who required moderate (≥ 5 units erythrocytes) received minimal (0-4 erythrocytes). Deformability measured samples drawn directly...
Local skin heating is used to assess microvascular function in clinical populations because NO required for full expression of the response; however, controversy exists as precise synthase (NOS) isoform producing NO. Human aging associated with attenuated cutaneous vasodilation but little known about middle aged, an age cohort comparison populations. We hypothesized that endothelial NOS (eNOS) primary mediating production during local heating, and eNOS-dependent would be reduced middle-aged...
Significance Non–image-forming opsins such as Opn4 regulate important physiological functions circadian photo-entrainment and affect. The recent discovery that melanopsin (Opn4) outside the central nervous system prompted us to explore a potential role for this receptor in blood vessel regulation. We hypothesized Opn4-mediated signaling might explain phenomenon of photorelaxation, which mechanism has remained elusive. report presence vessels demonstrate it mediates wavelength-specific,...
Glycosphingolipids, integral components of the cell membrane, have been shown to serve as messengers, transducing growth factor-initiated phenotypes. Here, we examined whether inhibition glycosphingolipid synthesis could ameliorate atherosclerosis and arterial stiffness in transgenic mice rabbits.Apolipoprotein E(-/-) (12 weeks age; n=6) were fed regular chow or a Western diet (1.25% cholesterol, 2% fat). Mice 5 10 mg/kg an inhibitor synthesis,...
The mechanisms by which nitric oxide (NO) influences myocardial Ca2+ cycling remain controversial. Because NO synthases (NOS) have specific spatial localization in cardiac myocytes, we hypothesized that neuronal NOS (NOS1) found sarcoplasmic reticulum (SR) preferentially regulates SR release and reuptake resulting potentiation of the force-frequency response (FFR). Transesophageal pacing (660 to 840 bpm) intact C57Bl/6 mice (WT) stimulated both contractility (dP/dtmax normalized...