Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome
Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Stellenbosch : University of Stellenbosch
2008
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613863450509312 |
|---|---|
| access_status_str | Open Access |
| author | Smith, Wayne |
| author2 | Du Toit, E. F. |
| author_browse | Du Toit, E. F. Smith, Wayne |
| author_facet | Du Toit, E. F. Smith, Wayne |
| author_sort | Smith, Wayne |
| collection | Thesis |
| dc_rights_str_mv | University of Stellenbosch |
| description | Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/2446 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:42:53.367Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2008 |
| publishDateRange | 2008 |
| publishDateSort | 2008 |
| publisher | Stellenbosch : University of Stellenbosch |
| publisherStr | Stellenbosch : University of Stellenbosch |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/2446 A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome Smith, Wayne Du Toit, E. F. Moolman, J. A. University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Medical Physiology. Metabolic syndrome Ischemia Reperfusion injury Angiotensin II Endothelins Obesity Rats as laboratory animals Cardiovascular system -- Diseases Dissertations -- Medicine Theses -- Medicine Dissertations -- Medical physiology Theses -- Medical physiology Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006. Introduction: Obesity, which is implicated in the development of the metabolic syndrome (MS) is reaching epidemic proportions worldwide. MS significantly increases the risk of developing cardiovascular disease, which includes coronary artery disease. The current absence of animal models of diet induced obesity and the MS makes the investigation of the cardiovascular consequences of MS virtually impossible. As a result the effects of the MS on cardiac function, morphology and susceptibility to ischaemia are not well understood. Aims: We set out to: 1) develop and characterize a rodent model of dietinduced obesity and the MS, 2) investigate the susceptibility of hearts from these animals to ischaemia/reperfusion induced injury and, 3) determine whether angiotensin II (Ang II) and endothelin-1 (ET-1) plays a role in cardiac remodelling and/or the severity of ischaemia and reperfusion injury in this model. Methods: Male Wistar rats were fed a standard rat chow diet or cafeteria diet (CD) for 16 weeks. After the feeding period rats were sacrificed and blood and myocardial tissue samples were collected to document biochemical changes in these animals. Hearts were perfused on the isolated working rat heart perfusion apparatus to assess myocardial mechanical function before and after ischaemia. In a separate series of experiments, hearts underwent coronary artery ligation to determine the incidence and duration of ventricular arrhythmias during ischaemia and reperfusion, using electrocardiography. To assess a possible link between myocardial remodelling and ischaemia/reperfusion injury and myocardial Ang II and ET-1 content, we also measured these peptides under basal conditions and during ischaemia. Two-dimensional targeted Mmode echocardiography was used to assess in vivo myocardial mechanical function in control and obese rats. Results: After 16 weeks on the CD, obese rats satisfied the World Health Organization (WHO) criteria for the MS by having visceral obesity, insulin resistance, dyslipidaemia and an elevated systolic blood pressure, compared to control rats. Circulating Ang II levels, but not ET-1 levels, were elevated in CD fed rats. Obese rats had cardiac hypertrophy and ex vivo basal myocardial mechanical function was depressed in the CD fed rat hearts compared to control rat hearts. CD fed rat hearts had poorer aortic output (AO) recoveries compared to hearts from control rats. These hearts also had a higher incidence and duration of reperfusion arrhythmias. No such functional differences were seen in the in vivo experiments. No differences in basal or ischaemic myocardial Ang II and ET-1 levels were seen in either group. Conclusion: We have developed and characterized a model of diet-induced obesity and the MS. Obesity is associated with cardiac hypertrophy and an increased myocardial susceptibility to ischaemia and reperfusion injury in our model. The hearts from obese rats were also more prone to reperfusion ventricular arrhythmias. As myocardial function was only poorer in the ex vivo obese animal experiments, our data suggests that the obesity associated changes in function observed in the ex vivo studies may be related to the absence of circulating substrates or factors, which are essential for their normal mechanical function. 2008-07-30T13:49:03Z 2010-06-01T08:48:55Z 2008-07-30T13:49:03Z 2010-06-01T08:48:55Z 2006-03 Thesis http://hdl.handle.net/10019.1/2446 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch |
| spellingShingle | Metabolic syndrome Ischemia Reperfusion injury Angiotensin II Endothelins Obesity Rats as laboratory animals Cardiovascular system -- Diseases Dissertations -- Medicine Theses -- Medicine Dissertations -- Medical physiology Theses -- Medical physiology Smith, Wayne A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title | A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title_full | A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title_fullStr | A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title_full_unstemmed | A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title_short | A pathologic role for angiotensin II and endothelin-1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| title_sort | pathologic role for angiotensin ii and endothelin 1 in cardiac remodelling and ischaemia and reperfusion injury in a rat model of the metabolic syndrome |
| topic | Metabolic syndrome Ischemia Reperfusion injury Angiotensin II Endothelins Obesity Rats as laboratory animals Cardiovascular system -- Diseases Dissertations -- Medicine Theses -- Medicine Dissertations -- Medical physiology Theses -- Medical physiology |
| url | http://hdl.handle.net/10019.1/2446 |
| work_keys_str_mv | AT smithwayne apathologicroleforangiotensiniiandendothelin1incardiacremodellingandischaemiaandreperfusioninjuryinaratmodelofthemetabolicsyndrome AT smithwayne pathologicroleforangiotensiniiandendothelin1incardiacremodellingandischaemiaandreperfusioninjuryinaratmodelofthemetabolicsyndrome |