title: Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy.
abstract: Metabolic disturbances and oxidative stress have been highlighted as potential causative factors for the development of diabetic cardiomyopathy. The β-blocker metoprolol is known to improve function in the diabetic rat heart and ameliorates the sequelae associated with oxidative stress, without lowering oxidative stress. The antioxidant ascorbic acid is known to improve function in the diabetic rat heart. We tested whether a combination of ascorbic acid and metoprolol treatment would improve function further than each drug individually. Control and streptozotocin-induced diabetic Wistar rats were treated with metoprolol (15 mg·(kg body mass)(-1)·day(-1), via an osmotic pump) and (or) ascorbic acid (1000 mg·(kg body mass)(-1)·day(-1), via their drinking water). To study the effect of treatment on the development of dysfunction, we examined time points before (5 weeks diabetic) and after (7 weeks diabetic) development of overt systolic dysfunction. Echocardiography and working-heart-perfusion were used to assess cardiac function. Blood and tissue samples were collected to assess the severity of disease and oxidative stress. While both drugs improved function, only ascorbic acid had effects on oxidative damage. Combination treatment had a more pronounced improvement in function. Our β-blocker + antioxidant treatment strategy focused on oxidative stress, not diabetes specifically; therefore, it may prove useful in other diseases where oxidative stress contributes to the pathology.
authors.affiliation: a James Hogg Research Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada.
authors.forename: Varun
authors.initials: V
authors.lastname: Saran
authors.forename: Vijay
authors.initials: V
authors.lastname: Sharma
authors.forename: Richard
authors.initials: R
authors.lastname: Wambolt
authors.forename: Violet G
authors.initials: VG
authors.lastname: Yuen
authors.forename: Michael
authors.initials: M
authors.lastname: Allard
authors.forename: John Hugh
authors.initials: JH
authors.lastname: McNeill
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D058065:Diabetic Cardiomyopathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D017208:Rats, Wistar
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000975:Antioxidants; D008790:Metoprolol; D001205:Ascorbic Acid
keywords: antioxidant; antioxydant; cardiac function; diabetes; diabète; fonction cardiaque; metabolism; métabolisme; oxidative stress; stress oxydant; β-blocker; β-bloquant