Advisor | Ables, Elizabeth Tweedie | |
Author | Byrum, Rachel | |
Date Accessioned | 2023-09-14T13:14:21Z | |
Date Created | 2023-07 | |
Date of Issue | 2023-08-08 | |
xmlui.metadata.dc.date.submitted | July 2023 | |
Identifier (URI) | http://hdl.handle.net/10342/13165 | |
Description | Hypertension is a prevalent and potentially deadly disease that affects approximately 116 million (47%) adults diagnosed in the U.S. as reported by the CDC in 2017. Understanding mechanisms responsible for high blood pressure, particularly, the Renin-Angiotensin-Aldosterone System (RAAS) may lead to better treatment options and preventative measures. The current study determines the local role of RAAS on heart muscle and evaluates the indirect Ca2+ homeostatic control of cardiac contractility during high blood pressure. The objectives are to study the expression of RAAS-mediated receptors and the membrane-bound Na/K ATPase (NKA) pump as it relates to the membrane-bound Sodium-Calcium exchanger (NCX). We assess the intracellular sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in the ventricular myocytes for calcium reuptake since NKA in association with NCX and SERCA may play a significant role in ventricular contractility. The results show a significant decrease in the protein expression for G protein-coupled receptor (GPCR), MAS1 proto-oncogene protein (MAS) for angiotensin 1-7 (Ang1-7) peptides in hypertension. Conversely, protein expression for angiotensin receptor type 1 (AT1R) was significantly higher in cardiomyocytes. While AT1R mediates the enhancement of cardiac contractility, MAS receptor mediates the metabolite of angiotensin II, through Ang1-7, and serves as the protective arm of angiotensin peptides. Further, the results show an increase in protein expression of cardiac membrane-bound NKA isoforms (1 and 2) in the hypertensive rodents, believed to have triggered intracellular calcium ([Ca2+] i) increase via NCX system. In addition, there was a diminution in Ca2+ reuptake pump by SERCA in the sarcoplasmic reticulum (SR) of cardiomyocytes in hypertensive rodents. This could explain increased contractility of the cardiomyocytes through excitation-contraction coupling and calcium-induced calcium release (CICR) mechanisms. The study is a groundwork understanding of cardiac dysfunction during hypertension and may lead to a treatment option and/or preventative measures for sustained blood pressure. | |
Mimetype | application/pdf | |
Language | en | |
Publisher | East Carolina University | |
Subject | Renin Angiotensin Aldosterone System | |
Subject | Calcium Homeostasis | |
Subject | Angiotensin II, Angiotensin (1-7) | |
Subject | Cardiomyocytes | |
Subject | Hypertension | |
Subject | High blood pressure | |
Subject | (mREN2)27 | |
Title | Myocardial Implications in Renin Angiotensin Aldosterone-Regulated Hypertension | |
Type | Master's Thesis | |
xmlui.metadata.dc.date.updated | 2023-09-12T17:51:14Z | |
Department | Biology | |
Embargo Terms | 2025-07-01 | |
xmlui.metadata.dc.degree.name | M.S. | |
xmlui.metadata.dc.degree.level | Masters | |
xmlui.metadata.dc.degree.discipline | MS-Molecular Biology & Biotech | |
xmlui.metadata.dc.degree.grantor | East Carolina University | |
xmlui.metadata.dc.degree.department | Biology | |
xmlui.metadata.dc.embargo.lift | 2025-07-01 | |
xmlui.metadata.dc.type.material | text | |