Abstract 13: Central Sympathoinhibition Abrogates Skeletal Muscle Fibrosis, Oxidative Stress and Autonomic Dysregulation in a Mouse Model of Muscular Dystrophy
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Abstract
Sarcoglycan mutations cause muscular dystrophy in humans. We recently demonstrated that sarcoglycan delta deficient (Sgcd-/-) mice with muscular dystrophy exhibit autonomic dysregulation [Hypertension 2010]. We hypothesized that excessive sympathetic activity contributes to skeletal muscle pathology, decreased locomotor activity and autonomic dysregulation in young (10-12 wks) Sgcd-/- mice. The centrally-acting sympathoinhibitory drug rilmenidine (RIL) was infused into the brain of control C57BL6 and Sgcd-/- mice by osmotic pump for 7-9 wks beginning at 3 wks of age (42 ng/g/hr, ICV). Separate groups of mice were infused with saline vehicle (VEH). Blood pressure (BP), heart rate (HR) and locomotor activity were measured by telemetry. Cardiac (HR responses to propranolol) and vasomotor (BP response to ganglionic blockade) sympathetic tone were increased in VEH-treated Sgcd-/- mice, and normalized by RIL (Table). The RIL-induced sympathoinhibition in Sgcd-/- mice was accompanied by increases in baroreflex sensitivity (BRS, sequence technique), cardiovagal tone (HR response to atropine) and activity, with no change in BP (Table). RIL also decreased oxidative stress (superoxide) by 56% and fibrosis in Sgcd-/- skeletal muscle. RIL did not affect measured variables in control mice (Table). In summary, RIL-induced sympathoinhibition decreased skeletal muscle pathology, increased locomotor activity and improved autonomic regulation in young Sgcd-/- mice. The results implicate increased sympathetic activity in the pathogenesis of muscular dystrophy, and suggest that targeting the brain to inhibit sympathetic activity may provide a novel therapeutic approach.
- © 2013 by American Heart Association, Inc.
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- Abstract 13: Central Sympathoinhibition Abrogates Skeletal Muscle Fibrosis, Oxidative Stress and Autonomic Dysregulation in a Mouse Model of Muscular DystrophyRasna Sabharwal and Mark W ChapleauHypertension. 2013;62:A13, originally published October 14, 2015
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