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Attenuation of adverse cardiac effects in prednisolone-treated delta-sarcoglycan-deficient mice by mineralocorticoid-receptor-antagonism

Lookup NU author(s): Dr Ralf Bauer, Dr Alison Blain, Liz Greally, Professor Hanns Lochmuller, Emerita Professor Katherine Bushby, Dr Guy MacGowanORCiD, Professor Volker StraubORCiD

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Abstract

We have tested the hypothesis that the adverse effects of glucocorticoids in the delta-sarcoglycan-deficient (Sgcd-null) mouse are due to additional mineralocorticoid effects. We investigated the effects of spironolactone, an unselective mineralocorticoid-receptor antagonist, on in vivo cardiac haemodynamics, cardiomyocyte damage and Fibrosis in prednisolone treated Sgcd-null mice. Oral spironolactone given to 8-week-old Sgcd-null non-steroid treated mice had beneficial effects on systolic function by improving myocardial contractility when assessed by pressure-volume loops. Given in combination with prednisolone, spironolactone prevented steroid-induced deterioration of cardiac haemodynamics and acute sarcolemmal damage but not cardiac fibrosis. This study demonstrates the beneficial effects of oral spironolactone on cardiac haemodynamics in Sgcd-null mice and its ability to prevent some of the adverse effects of glucocorticoids. (C) 2009 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Bauer R, Blain A, Greally E, Lochmuller H, Bushby K, MacGowan GA, Straub V

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2010

Volume: 20

Issue: 1

Pages: 21-28

Print publication date: 01/01/2010

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier Ltd

URL: http://dx.doi.org/10.1016/j.nmd.2009.10.003

DOI: 10.1016/j.nmd.2009.10.003

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