Atorvastatin improves systolic function, but does not prevent the development of dilated cardiomyopathy in streptozotocin-induced diabetic rats

Abstract

Whereas atorvastatin does not reverse ventricular dilatation, it does have a positive hemodynamic effect on the CV system of diabetic rats. This hemodynamic benefit is independent of cholesterol levels, and is observed concomitantly with reduced oxidative stress, vascular remodeling, and improved endothelial function. Together, these results suggest that atorvastatin decreases the workload on the heart and improves systolic performance in type 1 diabetic rats by reducing oxidative stress, vascular tone, and systemic vascular resistance.

Ginkgo biloba Leaf Extract Protects against Myocardial Injury via Attenuation of Endoplasmic Reticulum Stress in Streptozotocin‐Induced Diabetic ApoE−/− Mice

“…These indicated that interstitial collagen deposition, ERS-related apoptosis, and NF- κ B-mediated inflammation were induced in diabetic ApoE −/− mice. Consistent with the results of previous studies [ 15 , 16 , 19 , 24 ], atorvastatin treatment improved the histological abnormalities, fibrosis, and apoptosis of cardiomyocytes via inhibition of NF- κ B-induced inflammation and cleaved caspase-3-mediated apoptosis in the diabetic heart. To our knowledge, the present study is the first study to show that traditional Chinese medicine, GBE, could protect against diabetic myocardial injury, particularly apoptosis, myocardial fibrosis, and NF- κ B-mediated inflammation via inhibition of ERS-related apoptosis, as evidenced by the decrease in p-JNK, caspase-12, and cleaved caspase-3 expression.…”

“…Mice exhibiting plasma glucose levels > 12 mmol/L were considered diabetic and were used in the study ( n = 58) [ 13 , 14 ]. The diabetic mice were then treated with atorvastatin [ 15 , 16 ] (10 mg/kg/day, intragastric (i.g. ), n = 14), GBE at a low dose (200 mg/kg/day, i.g., n = 16), or GBE at a high dose (400 mg/kg/day, i.g., n = 17).…”

Synergistic Effects of Dantrolene and Nimodipine on the Phenylephrine-Induced Contraction and ACh-Induced Relaxation in Aortic Rings from Diabetic Rats

“…To determine the effect of 50 μ M dantrolene, 50 nM nimodipine, and the combination of these drugs on the endothelial-dependent relaxation, aortic rings were precontracted with phenylephrine (PHE, 1.0 μ M), following the protocol described previously [ 23 , 24 ]. When the maximal contraction reached a plateau, cumulative concentration-response curves (from 0.1 nM to 10 μ M) for ACh were generated.…”

“…The effects of dantrolene and nimodipine on lipid peroxidation, a marker of oxidative stress, were evaluated following the methods of Quidgley et al [ 23 ], by measuring vascular malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE) levels before and after a 30 min incubation period with dantrolene (50 μ M), nimodipine (50 nM), and these drugs in combination using a commercial kit (Bioxytech LPO-586; Oxis Research, Portland, OR). Briefly, homogenized tissues were centrifuged at 4°C for 10 min, and the supernatant was collected and stored at −80°C.…”

Targeting metabolic disturbance in the diabetic heart

“…While statins are one of the most prescribed drugs worldwide due to their effective and safe impact on cholesterol levels, they do not seem to affect the natural history of DCM and their repercussion on the diabetic myocardium is currently being investigated. Most animal evidence is based on STZ-treated animals, and it has been shown that a variety of statins successfully reverted the DCM phenotype (Table 1 ) [ 25 , 26 , 37 ]. Yet it remains unclear whether the improvement of cardiac performance is due mostly to decreased vascular remodeling and heart workload rather than to a direct cardiac effect.…”