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Angiotensin‐(1‐7) Delays Onset of Dilated Cardiomyopathy in Mice with Muscular Dystrophy
Author(s) -
Sabharwal Rasna,
Yang Liping
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.754.7
Subject(s) - medicine , endocrinology , angiotensin ii , dilated cardiomyopathy , ejection fraction , cardiac function curve , cardiomyopathy , blood pressure , heart rate , muscular dystrophy , cardiology , fibrosis , heart failure
We have demonstrated that angiotensin II‐induced autonomic and skeletal muscle dysfunction precedes and predicts development of dilated cardiomyopathy (DCM) and premature mortality in sarcoglycan‐delta deficient mice, i.e. murine model of muscular dystrophy [Exp Physiol 2015] . In addition, we have shown that ang‐(1‐7) administered for 8 weeks markedly improves autonomic function and locomotor activity in young (>15 weeks of age) Sgcd−/− mice by attenuating levels of circulating and skeletal muscle Ang‐II [Clin Sci 2014] . In this study, our goals were – (i) to determine whether Ang‐(1‐7) infusion delays onset of DCM in older mice (>50 weeks of age); and (ii) to evaluate the performance of the recently released SMP‐300 iPRECIO Infusion Pumps (Primetech Corporation ® , Japan) in delivering 500 ng of Ang‐(1‐7) at a rate 0.1 ml/hour for 49 days. Blood pressure (BP), heart rate (HR) and sympathovagal tone were measured by telemetry (PA‐C10, DSI ® ) in older control C57BL6 (untreated n=3) and Sgcd−/− (untreated n=4; treated n=4) mice. Compared to untreated control mice, untreated Sgcd−/− mice exhibit increased sympathetic tone (HR response to propranolol), reduced HR variability (parasympathetic tone), increased cardiac fibrosis (Masson's staining), and cardiac dysfunction (echocardiography) (all variables P<0.05). Ang‐(1‐7) effectively restored autonomic function, reduced cardiac fibrosis by 44%, increased ejection fraction by 21%, and reduced end‐diastolic volume/mass by 57% (P<0.05 vs. untreated Sgcd−/− mice). We conclude: 1) Ang‐(1‐7) treatment restores sympathovagal balance, reduces fibrosis and delays onset of DCM in older aged mice with muscular dystrophy. 2) iPRECIO infusion pumps are refillable, reprogrammable, and delivers drugs easily and successfully. 3) Albeit the combined weights of iPRECIO pump (3.3 g) and DSI transmitter (1.4 g) do not interfere with data collection, it is recommended to use mice not smaller than 25 g of body weight. Support or Funding Information Tarix Pharmaceuticals, Primetech, DSI