The antioxidant tempol attenuates pressure overload-induced cardiac hypertrophy and contractile dysfunction in mice fed a high-fructose diet

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 295; no. 6; pp. H2223 - H2230
• Main Authors: Chess, David J, Xu, Wenhong, Khairallah, Ramzi, O'Shea, Karen M, Kop, Willem J, Azimzadeh, Agnes M, Stanley, William C
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2008
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Biomarkers - metabolism; Cardiology; Cardiomegaly - etiology; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Cardiomegaly - prevention & control; Cardiotonic Agents - pharmacology; Cyclic N-Oxides - pharmacology; Diet; Dietary Carbohydrates; Disease Models, Animal; Fructose; Gene Expression Regulation, Enzymologic - drug effects; Heart; Hypertension - drug therapy; Hypertension - etiology; Hypertension - pathology; Hypertension - physiopathology; Lipid Peroxidation - drug effects; Male; Mice; Mice, Inbred C57BL; Myocardial Contraction - drug effects; Myocardium - enzymology; Myocardium - pathology; Oxidation; Oxidative Stress - drug effects; RNA, Messenger - metabolism; Rodents; Spin Labels; Sugar; Translational Physiology; Ventricular Remodeling - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00563.2008

Departments of 1 Physiology and Biophysics and 3 Nutrition, School of Medicine, Case Western Reserve University, Cleveland, Ohio; and Division of Cardiology, Departments of 2 Medicine and 4 Surgery, University of Maryland, Baltimore, Maryland Submitted 27 May 2008 ; accepted in final form 6 October 2008 We have previously shown that high-sugar diets increase mortality and left ventricular (LV) dysfunction during pressure overload. The mechanisms behind these diet-induced alterations are unclear but may involve increased oxidative stress in the myocardium. The present study examined whether high-fructose feeding increased myocardial oxidative damage and exacerbated systolic dysfunction after transverse aortic constriction (TAC) and if this effect could be attenuated by treatment with the antioxidant tempol. Immediately after surgery, TAC and sham mice were assigned to a high-starch diet (58% of total energy intake as cornstarch and 10% fat) or high-fructose diet (61% fructose and 10% fat) with or without the addition of tempol [0.1% (wt/wt) in the chow] and maintained on the treatment for 8 wk. In response to TAC, fructose-fed mice had greater cardiac hypertrophy (55.1% increase in the heart weight-to-tibia length ratio) than starch-fed mice (22.3% increase in the heart weight-to-tibia length ratio). Treatment with tempol significantly attenuated cardiac hypertrophy in fructose-fed TAC mice (18.3% increase in the heart weight-to-tibia ratio). Similarly, fructose-fed TAC mice had a decreased LV area of fractional shortening (from 38 ± 2% in sham to 22 ± 4% in TAC), which was prevented by tempol treatment (33 ± 3%). Markers of lipid peroxidation in fructose-fed TAC hearts were also blunted by tempol. In conclusion, tempol significantly blunted markers of cardiac hypertrophy, LV remodeling, contractile dysfunction, and oxidative stress in fructose-fed TAC mice. antioxidants; myocardial oxidative damage; systolic dysfunction Address for reprint requests and other correspondence: W. C. Stanley, Div. of Cardiology, Dept. of Medicine, Univ. of Maryland, 20 Penn St., HSF-2, Rm. S022, Baltimore, MD 21201 (e-mail: wstanley{at}medicine.umaryland.edu )