Reduction in advanced glycation end products by ACE inhibitor in diabetic cardiomyopathy model

Background: Advanced glycation end-products (AGEs) due to hyperglycemia have been reported with diabetic complications. The effect of angiotensin converting enzyme (ACE) inhibition on the formation of AGEs and oxidative stress in the myocardium was explored.

Methods: Streptozocin-induced diabetic rats were randomized to three groups including untreated, treated with ACE inhibitor captopril, and treated with aminoguanidine for 24 weeks with non-diabetic rats as control.

Results: At study end, elevations of blood pressure, heart to body weight ratio, and brain natriuretic peptide levels were found in diabetic rats, indicating cardiac hypertrophy and dysfunction. Accumulation of myocardial AGEs/ receptor of AGEs (RAGEs), as determined by immunohistochemistry and Western blots were increased in diabetic animals, which were attenuated by both captopril and aminoguanidine. Staining of nitrotyrosine and 8-hydroxydeaminoguanosine, markers of oxidative stress, also increased in diabetic rats and was attenuated by both captopril and aminoguanidine treatment. The myocardial pentosidine, a marker of AGEs, increased in diabetic rats but was not significantly affected by either treatment.

Conclusion: This study has identified a relationship between the renin-angiotensin system and the accumulation of AGEs in experimental diabetic hearts that may be linked through oxidative stress.