Cellular and Molecular Physiology Commons^™

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …

Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share …

The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients, Syed Ahmad Rizvi

Honors College Theses

While commonly known to be the organ that helps with urine production within the human body, the kidney plays one of the most crucial roles in maintaining homeostasis. When establishing all of the roles the kidney has on keeping humans healthy, there is the question of how does the body cope when a patient is diagnosed with kidney failure. One of the more common treatment options that allows the body to continue to function without a kidney is by beginning a patient on a form of dialysis. However, as with any treatment, there will always be a list of side …

Potential Role Of The Large Protein Titin In The Development Of Heart Failure, Mary M. Prickett

Senior Theses

I will be exploring the impact of the large protein Titin on heart failure with a preserved ejection fraction (HFpEF). It was hypothesized that myocardial Titin plays a significant role in the progression of HFpEF through isoform, N2BA and N2B, changes. It was hypothesized that an increase in the quantity of N2B Titin, less compliant, and a decrease in N2BA Titin, more compliant, will be observed as HF progresses, contributing to an increase in passive stiffness involved in heart contraction. I will cover a detailed report on the role of Titin in HFpEF and propose research methods to explore further.

Nanoformulation Of The Superoxide Dismutase Mimic, Mntnbuoe-2-Pyp5+, Prevents Its Acute Hypotensive Response, Sarah L. Schlichte, Svetlana Romanova, Kenichi Katsurada, Elizabeth A. Kosmacek, Tatiana K. Bronich, Kaushik K. Patel, Rebecca E. Oberley-Deegan, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Scavenging superoxide (O₂^•-) via overexpression of superoxide dismutase (SOD) or administration of SOD mimics improves outcomes in multiple experimental models of human disease including cardiovascular disease, neurodegeneration, and cancer. While few SOD mimics have transitioned to clinical trials, MnTnBuOE-2-PyP⁵⁺ (BuOE), a manganese porphyrin SOD mimic, is currently in clinical trials as a radioprotector for cancer patients; thus, providing hope for the use of SOD mimics in the clinical setting. However, BuOE transiently alters cardiovascular function including a significant and precipitous decrease in blood pressure. To limit BuOE's acute hypotensive action, we developed a mesoporous silica nanoparticle …

Glp-1 Mediated Diuresis And Natriuresis Are Blunted In Heart Failure And Restored By Selective Afferent Renal Denervation, Kenichi Katsurada, Shyam Sundar Nandi, Hong Zheng, Xuefei Liu, Neeru M. Sharma, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.

METHODS: HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total …

Kinetics Of Notch Signaling During Osteoclastogenesis, Amber Larissa Framstad

EWU Masters Thesis Collection

Bone remodeling, the process of removing and replacing damaged bone matrix, is a dynamic physiological process essential to maintaining bone composition and integrity. Improper coordination of resorption and formation can lead to pathologic changes in bone composition and quality, as is seen in osteoporosis, a bone disorder most seen in post-metapausal women attributed to decreased estrogen levels. The Notch signal pathway is a highly conserved direct cell communication pathway known to regulate cell proliferation, differentiation and survival in many cell types including the differentiation of osteoclasts from bone marrow macrophages (BMMs). Osteoclastogenesis is initiated in BMMs by receptor activator of …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Graduate Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb unloading …

Redox Biology In Physiology And Disease, Matthew C. Zimmerman, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

No abstract provided.

Redox-Sensitive Calcium/Calmodulin-Dependent Protein Kinase Iiα In Angiotensin Ii Intra-Neuronal Signaling And Hypertension, Urmi Basu, Adam J. Case, Jinxu Liu, Jun Tian, Yulong Li, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Dysregulation of brain angiotensin II (AngII) signaling results in modulation of neuronal ion channel activity, an increase in neuronal firing, enhanced sympathoexcitation, and subsequently elevated blood pressure. Studies over the past two decades have shown that these AngII responses are mediated, in part, by reactive oxygen species (ROS). However, the redox-sensitive target(s) that are directly acted upon by these ROS to execute the AngII pathophysiological responses in neurons remain unclear. Calcium/calmodulin-dependent protein kinase II (CaMKII) is an AngII-activated intra-neuronal signaling protein, which has been suggested to be redox sensitive as overexpressing the antioxidant enzyme superoxide dismutase attenuates AngII-induced activation of …

Central Glucagon-Like Peptide-1 Receptor Signaling Via Brainstem Catecholamine Neurons Counteracts Hypertension In Spontaneously Hypertensive Rats, Kenichi Katsurada, Masanori Nakata, Toshinobu Saito, Boyang Zhang, Yuko Maejima, Shyam Sundar Nandi, Neeru M. Sharma, Kaushik K. Patel, Kazuomi Kario, Toshihiko Yada

Journal Articles: Cellular & Integrative Physiology

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to …

Autonomic And Redox Imbalance Correlates With T-Lymphocyte Inflammation In A Model Of Chronic Social Defeat Stress, Cassandra M. Moshfegh, Safwan K. Elkhatib, Christopher W. Collins, Allison J. Kohl, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like …

Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch

Theses and Dissertations

The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …

The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert

Graduate School of Biomedical Sciences Theses and Dissertations

Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …

Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders To Resistance Exercise Training: Current Perspectives And Future Research Directions, Michael D. Roberts, Cody T. Haun, Christopher B. Mobley, Petey W. Mumford, Matthew A. Romero, Paul A. Roberson, Christopher G. Vann, John J. Mccarthy

Physiology Faculty Publications

Numerous reports suggest there are low and high skeletal muscle hypertrophic responders following weeks to months of structured resistance exercise training (referred to as low and high responders herein). Specifically, divergent alterations in muscle fiber cross sectional area (fCSA), vastus lateralis thickness, and whole body lean tissue mass have been shown to occur in high versus low responders. Differential responses in ribosome biogenesis and subsequent protein synthetic rates during training seemingly explain some of this individual variation in humans, and mechanistic in vitro and rodent studies provide further evidence that ribosome biogenesis is critical for muscle hypertrophy. High responders may …

Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …

Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung

PRECS 2018

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and …

Till Death Do Us Part: The Marriage Of Autophagy And Apoptosis., Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, …

Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application …

Direct Conversion Of Mouse Astrocytes Into Neural Progenitor Cells And Specific Lineages Of Neurons, Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C. Zheng

Journal Articles: Cellular & Integrative Physiology

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.

Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.

Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation …

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …

S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson

Journal Articles: Cellular & Integrative Physiology

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT) …

No Difference In Myosin Kinetics And Spatial Distribution Of The Lever Arm In The Left And Right Ventricles Of Human Hearts, Divya Duggal, S. Requena, Janhavi Nagwekar, Sangram Raut, Ryan Rich, Hriday Das, Vipul Patel, Ignacy Gryczynski, Rafal Fudala, Zygmunt Gryczynski, Cheavar Blair, Kenneth S. Campbell, Julian Borejdo

Physiology Faculty Publications

The systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles. Such a question cannot be answered by studying the entire ventricles or myocytes because any observed differences would be wiped out by averaging the information obtained from trillions of myosin molecules present in a ventricle or myocyte. …

Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, …

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in …