Abstract
Abstract 398: Angiotensin-[1-7] Infusion Reduces Skeletal Muscle Fibrosis and Restores Locomotor Activity and Sympathovagal Balance in a Mouse Model of Muscular Dystrophy
Hypertension (Dallas, Tex. 1979), Vol.60(suppl_1)
09/2012
DOI: 10.1161/hyp.60.suppl_1.A398
Abstract
Muscular dystrophy is a catastrophic, fatal neuromuscular disease in need of new therapies. Angiotensin II binding to AT
1
receptors (AT
1
R) contributes to fibrosis in dystrophic skeletal muscle and AT
1
R blockers are currently being tested in clinical trials. Recently, we reported that autonomic dysregulation precedes and predicts development of cardiomyopathy in sarcoglycan delta deficient (Sgcd-/-) mice with muscular dystrophy
(Clin Auton Res, 2010
). We hypothesized that infusion of the angiotensin peptide Ang-[1-7] will rescue skeletal muscle, locomotor, and autonomic nervous system phenotypes in young Sgcd-/- mice. Control and Sgcd-/- mice were infused with Ang-[1-7] (300 ng/kg/min) for 8 wks beginning at 3 wks of age. Blood pressure (BP), heart rate (HR) and activity were recorded by telemetry in treated and untreated mice. Baroreflex sensitivity (BRS, sequence technique) and resting cardiac vagal and sympathetic tone (HR responses to atropine and propranolol) were measured. BP, activity, BRS and vagal tone were lower in Sgcd-/-
vs.
control mice, whereas sympathetic tone was higher (Table). Ang-[1-7] normalized activity, BRS, and sympathovagal balance in Sgcd-/- mice without affecting BP, and did not influence any variable in control mice. Skeletal muscle fibrosis present in Sgcd-/- mice (18±1%, n=9) was markedly reduced by Ang-[1-7] (3±1%, n=5). We conclude that Ang-[1-7] reduces skeletal muscle fibrosis and restores locomotor activity and sympathovagal balance in Sgcd-/- mice, without lowering BP. Ang-[1-7] and/or enhancement of its endogenous production may provide a novel therapeutic approach to muscular dystrophy.
Details
- Title: Subtitle
- Abstract 398: Angiotensin-[1-7] Infusion Reduces Skeletal Muscle Fibrosis and Restores Locomotor Activity and Sympathovagal Balance in a Mouse Model of Muscular Dystrophy
- Creators
- Rasna Sabharwal - University of IowaMark W Chapleau - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.60(suppl_1)
- DOI
- 10.1161/hyp.60.suppl_1.A398
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2012
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984302190102771
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