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Title: Investigation of the cardiac endothelin system post myocardial infarction in the rat
Author: Sherry, L. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Survivors of acute myocardial infarction (MI) have a high risk of developing chronic heart failure (CHF). In human CHF there is evidence that plasma levels of the potent vasoconstrictor peptide, endothelin (ET)-1 and its precursor big ET-1 are increased, correlate positively with disease severity, and may be important predictors of outcome. The aims of this thesis were to investigate the heart as a source of ET-1 synthesis and to investigate the role of the cardiac ET-1 system during scar formation in the early stages post-MI and also during progression of CHF in a rat model. MI in the rat was induced by surgical ligation of the left anterior descending coronary artery. The myocardial ET system was investigated using immunohistochemical and in situ hybridisation techniques. In the normal heart, immunoreactive ET-1 was identified in the vascular endothelium and myoendothelial cells in the myocardium. Staining for ET-1 was intense and uniform in cardiomyocytes throughout the myocardium. In situ hybridisation confirmed that sites of preproET-1 mRNA expression coincided with sites of immunoreactive ET-1. These results indicate that the myocardium has the capacity to endogenously produce ET-1 in both myoendothelial cells and cardiomyocytes. Investigation of ET-1 immunoreactivity during scar formation 2, 7 and 14 days post-MI indicated an early transient increase in ET-1 in the infarct, which peaks at 7 days. At this time point, ET-1 could be localised to proliferating fibroblasts, infiltrating inflammatory cells and in the endothelia of newly forming vessels, suggesting a role for ET-1 in scar formation early post-MI. Though increased ET-1 staining could be localised at a cellular level in the developing infarct, further studies were needed to identify whether ET-1 was beneficial or detrimental during scar formation. Therefore, the effect on early stage scar formation of an ETA/B receptor antagonist (A-182086) fed to rats immediately after coronary artery ligation surgery and for the duration (2, 7 or 14 days) of the study was investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available