Systems and Integrative Physiology Commons^™

Physiological Development Of Hypertension As A Result Of High-Fat Diet Induced Obesity, Michael Nguyen

Williams Honors College, Honors Research Projects

This literature review focuses on the physiological development of obesity due to the consumption of diets rich in fats and the resulting pathophysiological development of hypertension. This review aims to identify causes of obesity and hypertension as well as current treatments to propose future areas of study. The literature review analyzed a wide variety of literature sources on obesity and hypertension published between the years 1995 and 2025. The review identifies high-fat diets as a cause of obesity and the resulting health effects of elevated leptin, insulin, and nervous system activity as contributors to the development of hypertension. Future areas …

Food Security And Its Impact On Hypertension In Urban Communities, Lauren M. Nobriga

Master's Projects and Capstones

The Quality Improvement Team proposed an intervention to increase enrollment in the Food Security Program, a six-month initiative that provides vouchers redeemable for fruits and vegetables. Long-term impacts of this Program include an improved food economy and enhanced patient disease management autonomy. This project aimed to increase the percentage of eligible adult medicine clinic patients enrolled in the Food Security Program by 25%, or 11 patients per month, based on the mean enrollment for the first four months of the Program (May to August) of nine patients. The intervention was based on bi-monthly performance reports, making the goal include enrolling …

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 …

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 …

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 …

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 …

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 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 …

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 …

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 …