Corticosteroid hormone action in the cardiovascular system

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http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/3449 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/3449 http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/3449 archive 4031 disk0/00/00/14/36 2011-03-15 12:32:35 2019-01-17 17:06:58 2011-07-19 16:36:02 thesis show 0 Hammer Fabian Stewart Paul M University of Birmingham Corticosteroid hormone action in the cardiovascular system unpub R1 QP RC 10col_mede The cardiovascular system (CVS) has emerged as an important target of corticosteroid hormones. Mineralocorticoid receptor antagonists provide cardiovascular protection and are now routinely used in disorders such as primary hyperaldosteronism, resistant hypertension and congestive heart failure (CHF) but the underlying molecular mechanisms of corticosteroid hormone action remain unclear. We have characterised corticosteroid hormone action and metabolism by 11β- hydroxysteroid-dehydrogenases (11β-HSDs) in isolated adult rat cardiomyocytes (CM) and cardiac fibroblasts (cFb). We have detected 11β-HSD1 expression and activity in CM and cFb where it facilitates glucocorticoid hormone action, whereas 11β-HSD2 was absent. We have shown differential gene regulation by aldosterone (Aldo) and corticosterone in CM and identified novel Aldo target genes which may provide insights into the molecular mechanisms of Aldo action. We have also studied the role of corticosteroids in essential hypertension and the effect of spironolactone (Spiro) upon their secretion and metabolism in patients with chronic kidney disease. We have shown that mineralocorticoids but not glucocorticoids are involved in elevated blood pressure in essential hypertension and that Spiro treatment results in compensatory activation of the renin-angiotensinaldosterone system (RAAS), whereas glucocorticoid secretion and metabolism remain unchanged. In summary, these data provide novel molecular and clinical insights into corticosteroid hormone action in the CVS. 2011-07 2010-09 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 243 University of Birmingham School of Clinical and Experimental Medicine d_ph mrc 2011-07 graduation