OBJECTIVE: Diabetic cardiomyopathy is an increasingly recognized cause of 
cardiac failure despite preserved left ventricular systolic function. Given the 
over-expression of angiotensin II in human diabetic cardiomyopathy, we 
hypothesized that combining hyperglycaemia with an enhanced tissue 
renin-angiotensin system would lead to the development of diastolic dysfunction 
with adverse remodeling in a rodent model.
METHODS: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats 
were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) 
and followed for 6 weeks. Prior to tissue collection, animals underwent 
pressure-volume loop acquisition.
RESULTS: Diabetic Ren-2 rats developed impairment of both active and passive 
phases of diastole, accompanied by reductions in SERCA-2a ATPase and 
phospholamban along with activation of the fetal gene program. Structural 
features of diabetic cardiomyopathy in the Ren-2 rat included interstitial 
fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with 
increased activity of transforming growth factor-beta (p<0.01 compared with 
non-diabetic Ren-2 rats for all parameters). No significant functional or 
structural derangements were observed in non-transgenic, SD diabetic rats.
CONCLUSION: These findings indicate that the combination of enhanced tissue 
renin-angiotensin system and hyperglycaemia lead to the development of diabetic 
cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this 
model, may be a consequence of activation of the pro-sclerotic cytokine, 
transforming growth factor-beta, by the diabetic state.