Journal
NEUROMUSCULAR DISORDERS
Volume 20, Issue 1, Pages 21-28Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2009.10.003
Keywords
Spironolactone; Glucocorticoids; delta-Sarcoglycan; Cardiomyopathy muscular dystrophy
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Funding
- Heart Research UK
- Newcastle University Hospitals
- German Ministry of Education and Research (BMBF, Bonn, Germany)
- BMBF [MD-NET 01GM0601]
- Medical Research Council [G0601943] Funding Source: researchfish
- MRC [G0601943] Funding Source: UKRI
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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.
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