| Summary: | Myocardial dysfunction and coronary macro/microvascular alterations are the hallmarks of diabetic cardiomyopathy and are ascribed to increased oxidative stress and altered nitric oxide synthase (NOS) activity. We hypothesize that pretreatment by cobalt-protoporphyrin IX (CoPP) ameliorates both myocardial function and coronary circulation in streptozotocin(STZ)-induced diabetic rats. Isolated hearts from diabetic rats in Langendorff configuration displayed lower left ventricular (LV) function and higher coronary resistance (CR) compared to hearts from control animals. CoPP treatment of diabetic animals (0.3mg/100g body weight i.p., once a week for three weeks) significantly increased all the contractile/relaxation indexes (p<0.01), while decreasing CR (p<0.01). CoPP enhanced HO-1 protein levels and reduced oxidative/nitrosative stress in diabetic animals, as indicated by the significant (p<0.05) decrease in heart GSSG/GSHtotal, O2-, malondialdehyde (MDA), and 3-nitrotyrosine levels. CoPP increased adiponectin levels and phosphorylation of AKT and AMPK and reversed the eNOS/iNOS expression imbalance observed in the untreated diabetic heart. Furthermore, after CoPP treatment, a rise in malonylCoA as well as a decrease in acetylCoA was observed in diabetic hearts. In this experimental model of diabetic cardiomyopathy, CoPP treatment improved both cardiac function and coronary flow by blunting oxidative/nitrosative stress, restoring eNOS/ iNOS expression balance and increasing HO-1 levels, thereby favoring improvement in both endothelial function and insulin sensitivity.
|
|---|
