Attenuation of adverse cardiac effects in prednisolone-treated delta-sarcoglycan-deficient mice by mineralocorticoid-receptor-antagonism.
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.
Bauer
Ralf
R
Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.
Blain
Alison
A
Greally
Elizabeth
E
Lochmüller
Hanns
H
Bushby
Kate
K
MacGowan
Guy A
GA
Straub
Volker
V
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size; D011239:Prednisolone / Q000009:adverse effects* / Q000627:therapeutic use; D049031:Sarcoglycans / Q000172:deficiency* / Q000235:genetics; D012508:Sarcolemma / Q000187:drug effects; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D049031:Sarcoglycans; D013148:Spironolactone; D011239:Prednisolone