Author(s): Stadler K, Jenei V, Somogyi A, Jakus J
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Abstract The effect and possible mechanisms of action of aminoguanidine (a preferential iNOS inhibitor) has been studied on cardiovascular damages and overproduction of reactive nitrogen species in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: 40 rats were divided into five groups (control and diabetic, with or without aminoguanidine treatment, diabetic with insulin treatment) and oxidative stress parameters were examined. Tissue nitric oxide levels were determined by EPR spectroscopy, while peroxynitrite generation by a chemiluminescence method. Cardiac hypertrophy, blood metabolic parameters (blood glucose, HbA1c, fructosamine), as well as tissue protein carbonyl levels were also determined. RESULTS: Diabetic animals showed increased nitric oxide and peroxynitrite generation in the aorta along with a significant hypertrophy and protein carbonylation of the cardiac tissue. Both aminoguanidine and insulin treatment suppressed high levels of nitric oxide and peroxynitrite in the vasculature, but only aminoguanidine was able to prevent hypertrophic alterations and to reduce protein carbonylation in the heart. CONCLUSIONS: The results show that (1) aminoguanidine reduces nitric oxide production and prevents cardiac hypertrophy, (2) insulin therapy improves carbohydrate metabolism, reduces nitrosative stress but has no effect on cardiac hypertrophy. Cardiac hypertrophy in diabetes is strongly correlated with non-enzymatic glycation. Aminoguanidine prevented hypertrophy by blocking the formation of advanced glycation end products rather than via other mechanisms.
This article was published in Orv Hetil
and referenced in Biology and Medicine