Mineralocorticoid Receptor Antagonists in Muscular Dystrophy Mice During Aging and Exercise

• DOI: 10.3233/jnd-180323
• Publication Date: 2018-07-13T17:47:28Z
• Authors: Jeovanna Lowe; Feni K. Kadakia; Jonathan G. Zins; Michael Haupt; Kyra K. Peczkowski; Neha Rastogi; Kyle T. Floyd; Elise P. Gomez-Sa...; Celso E. Gomez-Sa...; Mohammad T. Elnakish; Jill A. Rafael-Fo...; Paul M.L. Janssen
• Keywords: Mineralocorticoid; mdx mouse; Lisinopril

Mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors have shown preclinical efficacy for both skeletal and cardiac muscle outcomes in young sedentary dystrophin-deficient mdx mice also haploinsufficient utrophin, a Duchenne muscular dystrophy (DMD) model. The genotypic DMD model has mild pathology, making non-curative therapeutic effects difficult distinguish at baseline. Since the benefit of mineralocorticoid been translated patients, it is important optimize potential advantages by further defining parameters.We aimed test whether are detectable using three different reported methods exacerbating phenotype.We tested treatment with lisinopril antagonist spironolactone in: 10 week-old exercised, 1 year-old sedentary, 5 month-old isoproterenol treated performed comprehensive functional histological measurements.None protocols exacerbate phenotypes resulted dramatically enhanced pathology no significant was observed treatment.Since endogenous aldosterone production from immune cells dystrophic may explain efficacy, likely that these drugs work optimally during narrow window peak inflammation mice. Exercised aged do not display prolific damage inflammation, explaining absence continued drugs. more prevalent patients be longer.