Life Sciences Commons^™

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Sleep And Risk For Metabolic Syndrome, Hypertension, Diabetes And Obesity Among Community-Dwelling Older Adults, Philip Zendels, Trudy L. Moore-Harrison, Jane F. Gaultney

International Journal of Exercise Science

International Journal of Exercise Science 15(3): 88-102, 2022. Older adults often face a variety of health problems that are found less frequently in younger populations. Metabolic syndrome and other related diseases are common due to a variety of age and lifestyle factors. Sleep, often operationalized only as duration, quality, or apnea diagnosis, is associated with worse health outcomes across the lifespan. However, sleep is multi-faceted and may require a collection of measures in order to reflect this. This study examined a suite of self-reported sleep habits (risk for sleep apnea, night time duration, nap duration, quality, timing, and consistency of …

Mechanism Of The Superoxide Dismutase Mimic Mntnbuoe-2-Pyp5+ And Its Nanoformulation On Blood Pressure Regulation, Sarah L. Schlichte

Theses & Dissertations

It is well-established that reactive oxygen species (ROS), particularly superoxide (O₂^·-), produced in the vasculature and brain contribute to the pathogenesis of hypertension. We, and others, have previously reported that in vivo scavenging of O₂^·- via overexpression of superoxide dismutase (SOD) protein or SOD mimics decreases blood pressure in hypertensive animals. While few SOD mimics have transitioned to clinical trials, MnTnBuOE-2-PyP⁵⁺ (BuOE), a manganese porphyrin SOD mimic, is currently in clinical trials for normal tissue protection in cancer patients exposed to radiation therapy. Furthermore, our collaborators developed a nanoformulated BuOE (nanoBuOE) in which BuOE …

Characterization Of Spontaneous Preeclampsia In The African Green Monkey (Chlorocebus Aethiops Sabaeus), Chelsea Christina Weaver

Theses and Dissertations--Biology

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic …

Cardio-Renal Mechanisms Of Fructose-Induced Salt-Sensitive Hypertension, Peter Eric Levanovich

Wayne State University Dissertations

Dietary consumption of fructose facilitates increased intestinal fluid absorption and renal sodium reabsorption, thereby increasing fluid retention. The net result of this is a sustained increased in extracellular fluid volume that leads to states of hypervolemia and subsequent hypertension. Simultaneously, arterial pressure is being elevated by increased autonomic drive stemming from the sympathetic nervous system and various other endovascular proteins that induce vasoconstriction. Under these conditions, the addition of high dietary sodium promotes hypertension prior to the development of significant metabolic disturbances; the subtlety of which may go unnoticed by patients for prolonged periods. While much is understood regarding the …

Neurogenic Hypertension Mediated Mitochondrial Abnormality Leads To Cardiomyopathy: Contribution Of Upr Mt And Norepinephrine-Mir- 18a-5p-Hif-1Α Axis, Shyam Sundar Nandi, Kenichi Katsurada, Sushil K. Mahata, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Aims: Hypertension increases the risk of heart disease. Hallmark features of hypertensive heart disease is sympathoexcitation and cardiac mitochondrial abnormality. However, the molecular mechanisms for specifically neurally mediated mitochondrial abnormality and subsequent cardiac dysfunction are unclear. We hypothesized that enhanced sympatho-excitation to the heart elicits cardiac miR-18a-5p/HIF-1α and mitochondrial unfolded protein response (UPR^mt) signaling that lead to mitochondrial abnormalities and consequent pathological cardiac remodeling. Methods and Results: Using a model of neurogenic hypertension (NG-HTN), induced by intracerebroventricular (ICV) infusion of Ang II (NG-HTN; 20 ng/min, 14 days, 0.5 μl/h, or Saline; Control, 0.9%) through osmotic mini-pumps in Sprague-Dawley …

Effects Of Voluntary Exercise On Pressure-Induced Natriuresis In Hypertensive Female And Male Rats, Keshari Sudasinghe

All Graduate Theses, Dissertations, and Other Capstone Projects

Hypertension (HT) is one of the major diseases associated with the circulatory system and remains a public health problem with a high rate of prevalence in the adult population in the USA. The pressure natriuresis mechanism which is Na+ excretion in respond to rise in blood pressure acts as a long-term regulator of arterial blood pressure. Recent studies have demonstrated that impairment of this long-term pressure natriuresis mechanism is involved in hypertension (HT) and many other renal disorders. Exercise is a nonpharmacological treatment to help control HT, and exercise has a beneficial effect on vascular health, endothelial functions, arterial stiffness, …

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 …

Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

The Orexin System In Doca-Salt Hypertension: Regulation Of Vasopressin, Jeremy Bigalke

Dissertations, Master's Theses and Master's Reports

Orexin is a neuropeptide with a large range of functions, with a recently discovered role in blood pressure (BP) regulation. Although the role of brain orexin system in hypertension has been investigated in several hypertensive animals, it remains unclear whether activation of the orexin system contributes to the development of Deoxycorticosterone-acetate (DOCA) hypertension, an animal model of human salt sensitive hypertension. In this study, we investigated the hypothesis that Orexin-1 receptor (OX1R) expression is increased in the paraventricular nucleus (PVN), a critical brain area controlling cardiovascular function, which subsequently increases vasopressin (AVP) expression and peripheral secretion, resulting in hypertension development …

The Balance Between Prostaglandin E2 Ep3 And Ep4 Receptors Determines Severity Of Cardiac Damage In Myocardial Infarction And An Angiotensin Ii-Induced Model Of Hypertension, Timothy Dean Bryson

Wayne State University Dissertations

According to the center for disease control about 610,000 people die every year in the United States from heart disease, of which, coronary heart disease is the most common form. One major risk factor for heart attack is hypertension, which affects nearly half of all Americans [472, 473]. PGE2 plays an important role in regulating cardiovascular function and mediating inflammation, both of which contribute to the development of hypertension and/or heart disease. Prostaglandin E2 can act as a vasodilator or vasoconstrictor depending on which of its receptor subtypes are activated.

In general, activation of the EP1 and EP3 receptors is …

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 …

The Effect Of Dorsal Rhizotomy On Renal Sodium Excretion Following Dorsal Spinal Stimulation, Tanko Tijani Ahmed

All Graduate Theses, Dissertations, and Other Capstone Projects

Hypertension is one of the most common risk factors in the development of heart disease, stroke and end stage renal failure. Sympathetic overactivity is believed to be one of the main mechanism behind resistant hypertension. Renal denervation has been used to treat resistant hypertension, although this procedure is an invasive one. Spinal cord stimulation (SCS) is a known modality to treat ischemic pain, angina pectoris, and peripheral vascular diseases. In previous studies in this laboratory, unilateral spinal cord stimulation in spontaneously hypertensive rat (SHR) at 67% of the motor threshold increased urinary sodium and water excretion significantly, without affecting mean …

Effect Of Administration Of Somatostatin Analogue On Blood Pressure In Chronic Intermittent Hypoxic Rats, Kajal Kamra

Browse all Theses and Dissertations

The cardiorespiratory system in our bodies does not adapt to Chronic Intermittent Hypoxia (CIH) and consequently syndromes such as sleep apnea lead to pathophysiological conditions like Hypertension. It has been demonstrated that the peripheral chemoreceptors underpin the development of these conditions and at present, there are no selective drug therapies for this form of hypertension. However, evidence suggests that peripheral chemoreflex sensitivity to CO2 & hypoxia is reduced by Somatostatin (SST) in humans. Our preliminary in-vitro studies have demonstrated that SST will blunt the response of the carotid body to hypoxia and decrease the baseline activity of the carotid body. …

Functional Changes Associated With Shroom3 Deficiency And Mutation: Implications In Renal Pathophysiology And Disease, Doyun Ko

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) is a substantial global health burden that has recently been linked to the genetic locus SHROOM3 by several genome-wide association studies. Shroom3 is an actin-binding protein that is necessary for inducing apical constriction in epithelial cells. Our lab has previously shown that Shroom3 is critical for proper kidney development and loss of Shroom3 produces symptoms associated with CKD. As hypertension is both a leading cause and comorbidity of CKD, I hypothesized that loss of Shroom3 confers increased susceptibility to hypertension. Using a high-salt induced model of hypertension, I show that Shroom3 deficient mice do not become …

Autonomic Dysreflexia After Spinal Cord Injury: Systemic Pathophysiology And Methods Of Management, Khalid C. Eldahan, Alexander G. Rabchevsky

Physiology Faculty Publications

Traumatic spinal cord injury (SCI) has widespread physiological effects beyond the disruption of sensory and motor function, notably the loss of normal autonomic and cardiovascular control. Injury at or above the sixth thoracic spinal cord segment segregates critical spinal sympathetic neurons from supraspinal modulation which can result in a syndrome known as autonomic dysreflexia (AD). AD is defined as episodic hypertension and concomitant baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in the decentralized cord. This condition is often triggered by noxious yet unperceived visceral or somatic stimuli below the injury level and if severe enough can require immediate medical attention. …

Characterization Of Spontaneous Hypertension In Chlorocebus Aethiops Sabaeus, The African Green Monkey, Megan K. Rhoads

Theses and Dissertations--Biology

Hypertension is a complex multifactorial pathology that is a major risk factor for the development of cardiovascular disease, stroke, and end stage renal disease. In the United States, hypertension affects over 1 in 3 adults and comprises an annual cost of over $58 billion in the healthcare industry. While remarkable strides in the diagnosis and treatment of hypertension have been made since the pathology was first treated in the 1960s, a remarkable 13% of patients with elevated blood pressures are classified as resistant hypertensive, where blood pressure remains uncontrolled while on three or more classes of anti-hypertensive drugs. This treatment …

The Role Of Alström Syndrome 1 (Alms1) In Hypertension, Salt Sensitivity And Metabolic Syndrome, Keyona Nicole King-Medina

Wayne State University Dissertations

In humans, inactivating mutations in the Alström syndrome 1 (ALMS1) gene cause obesity, insulin resistance and hypertension (metabolic syndrome). More so, SNPs in the ALMS1 gene have been associated with kidney disease and cardiovascular disease. The

mechanisms causing these alterations are unclear. We recently found that the ALMS1 is expressed in the kidney thick ascending limb (TAL) where it mediates endocytosis of the renal Na/K/2Cl cotransporter termed NKCC2. To study the role of ALMS1 in renal

physiology we generated ALMS1 knockout (KO) rats in a Dahl salt-sensitive genetic background via zinc-finger nuclease targeting. We previously found that the amount of …

Glomerular Hyperfiltration And Hypertension In Diabetes, Jie Zhang

USF Tampa Graduate Theses and Dissertations

In the present study, we investigated the pathophysiological mechanisms of the hemodynamic alteration in diabetes. Glomerular hyperfiltration occurs in the early stage of diabetes mellitus and has been recognized to promote the pathogenesis of diabetic nephropathy. We determine the role of TGF response and the vascular tone of Af-Art in diabetic hyperfiltration and we found that 1) tubular high glucose directly activates NOS1 and increases NO generation in the macula densa, which inhibits TGF response and increases GFR; 2) high glucose dilates renal Af-Art through GLUT1 and mediated by NOS3-derived NO generation; 3) in diabetes, blunted TGF mediated by NOS1 …

The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

Role Of Alström Syndrome 1 (Alms1) In Nkcc2 Endocytosis, Thick Ascending Limb Function, Blood Pressure Regulation And Metabolic Function, Ankita Bachhawat Jaykumar

Wayne State University Dissertations

NaCl absorption by the Thick Ascending Limb (TAL) is mediated by the apical Na+/K+/2Cl- co-transporter, NKCC2. Increased NKCC2 activity and apical trafficking are associated to salt sensitive hypertension in rodents and humans. NKCC2 endocytosis is important for maintaining surface NKCC2 such that blocking NKCC2 endocytosis increased NKCC2 surface abundance and NKCC2-mediated NaCl reabsorption. Despite its importance, NKCC2 endocytosis has been poorly studied and a part of the reason may be attributed to the lack of availability of methods with good time resolution. Hence, we developed a method to image apical NKCC2 to monitor its endocytosis in real-time by Total Internal …

Po2 Dependence Of Oxygen Consumption In Skeletal Muscle Of Hypertensive And Normotensive Rats, Habiba Shah

Theses and Dissertations

Human essential hypertension affects over 75 million people in the United States, and can lead to death due to its several serious health complications such as hypertension-related cardiovascular disease. The purpose of this research was to understand how hypertension could cause physiological changes to the microcirculation, specifically the PO₂ dependence of oxygen consumption (VO₂) in skeletal muscle of normotensive and hypertensive rats. The Spontaneously Hypertensive Rat (SHR) strain was used as the diseased model, and Wistar-Kyoto (WKY) rats were used as controls to conduct this study. The SHR strain develops hypertension between 5-6 weeks after birth with …

Effects Of An 18- Week Strength, Conditioning, And Circuit Training Program On Weight Loss In A Middle Aged Adult Male, Aryeh D. Spingarn

Publications and Research

Aryeh Spingarn Queens College, City University of New York Department of Family, Nutrition, and Exercise Sciences, Effects of an 18-week strength, conditioning, and circuit training program on weight loss in a middle-aged male. Purpose: The purpose of this study was to examine the effects of a strength, conditioning, and circuit training program on weight loss in a middle age adult. Methods: The subject participated in an 18-week strength and conditioning program 2 days per week for one hour per session, totaling 2 hours of training time per week. The first 12 weeks of the program included only strength training for …

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Joseph I. Shapiro Md

Joseph I Shapiro MD

Schematic showing Na/K‐ATPase as reactive oxygen species (ROS) amplifier system. CTS‐cardiotonic steroids, Orange dimer is Na/K‐ATPase. pNaKtide refers to peptide formed from epitope of Na/K‐ATPase a1 subunit known to bind Src tyrosine kinase fused with TAT leader sequence.

The Effect Of Cardiowaves Interval Training On Resting Blood Pressure, Resting Heart Rate, And Mind-Body Wellness, Camilla M. Nielson, Barbara D. Lockhart, Ronald L. Hager, James D. George, Dennis L. Eggett, Patrick R. Steffen, Ulrike H. Mitchell, Bruce W. Bailey

International Journal of Exercise Science

International Journal of Exercise Science 9(1): 89-100, 2016. An experimental study to examine the effects of CardioWaves interval training (CWIT) and continuous training (CT) on resting blood pressure, resting heart rate, and mind-body wellness. Fifty-two normotensive (blood pressure <120/80 mmHg), pre-hypertensive (120–139/80–89 mmHg), and hypertensive (>140/90 mmHg) participants were randomly assigned and equally divided between the CWIT and CT groups. Both groups participated in the assigned exercise protocol 30 minutes per day, four days per week for eight weeks. Resting blood pressure, resting heart rate, and mind-body wellness were measured pre- and post-intervention. A total of 47 participants (15 females and 32 males) were included in the …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen

Journal of Undergraduate Research at Minnesota State University, Mankato

In this project, we developed a Western blotting procedure to semi-quantitate levels of 11β-HSD1 and 11β-HSD2 in whole cell extracts. Then, we applied this technique to analyze the effect of reduced maternal aldosterone levels on the expression of 11β-HSD1 and 11β-HSD2 isoenzymes in the placental tissue in both normal and hypertensive rats. These enzymes control levels of glucocorticoids which compete for aldosterone’s mineralocorticoid receptor. Overstimulation of this receptor results in hypertension. If aldosterone levels decrease, levels of the enzymes controlling active glucocorticoid concentrations might change to compensate for the lowered aldosterone levels. Decreased placental 11β-HSD2 expression could affect hypertension in …

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …

Muscle Metaboreflex Control Of Cardiovascular Function In Hypertension, Marty Daniel Spranger

Wayne State University Dissertations

Skeletal muscle ischemia during or immediately following exercise leads to the accumulation of metabolites (e.g., lactate, proton and diprotonated phosphate) which activate chemoreceptive afferents within the muscle leading to a reflex increase in sympathetic outflow generating substantial increases in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) - termed the muscle metaboreflex. When the reflex is activated during submaximal dynamic exercise, the pressor response occurs via increased CO with no net peripheral vasoconstriction. When metaboreflex activation is sustained during the recovery from exercise (i.e., post-exercise muscle ischemia - (PEMI)), whereas MAP remains elevated for as long as …