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Simvastatin, Atorvastatin, and Pravastatin Equally Improve Cardiovascular Status in Diabetic Rats by Improving Endothelial Function, and Reducing Perivascular Fibrosis and Oxidative Stress
Author(s) -
Quidgley Jose,
Crespo Maria,
Cruz Nildris
Publication year - 2015
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.29.1_supplement.626.2
Subject(s) - pravastatin , medicine , simvastatin , atorvastatin , endocrinology , diabetes mellitus , oxidative stress , endothelial dysfunction , fibrosis , cardiac function curve , statin , cholesterol , lipid profile , heart failure
Statins improve cardiovascular (CV) status of diabetic patients, regardless of their cholesterol levels. It remains unclear whether this effect is drug‐specific or class‐dependent,and the underlying mechanisms involved. We compared the effects of a low dose (10 mg/kg/day) of atorvastatin (AV), simvastatin (SV), and pravastatin (PV) over a four‐week period on cardiac performance in streptozotocin‐induced diabetic rats. Age‐matched, non‐diabetic rats were used as controls (CT). Echocardiographic variables, systolic blood pressure (SBP), acetylcholine (ACh)‐induced relaxation, plasma cholesterol levels, perivascular fibrosis, and oxidative‐stress markers MDA and 4‐HAE were measured. Cholesterol levels (mg/dl) were higher in diabetic rats than in CT (248.68 ± 15.78 vs. 156.01 ± 7.32, n = 8, P<0.05), and were not modified by any statin at this low dose. All three statins significantly reduced SBP in diabetic rats. Ejection fraction, stroke volume, and cardiac output index were lower in untreated diabetic rats than in CT (n = 10, P<0.05). All three statins significantly increased these CV parameters (n = 10, P<0.05). In addition, statins improved E Max values for the ACh‐induced relaxation, decreased media thickness, perivascular fibrosis, and both MDA and 4‐HAE in the aortas of diabetic rats. Together, our results indicate that in diabetic rats, AV, SV, and PV are equally effective in improving CV performance. The observed hemodynamic benefits are cholesterol‐independent, and appear to be secondary to improved endothelial function, and to reduced vascular tone and remodeling resulting from decreased oxidative stress. Supported by MBRS‐RISE R25‐GM061838.