Background: The study focused on investigating the effect of aminoguanidine on cardiovascular damages in diabetes and the possible mechanisms of its action.
Methods: Aminoguanidine (AMNG) was used to treat streptozotocin-induced diabetic rats, and the effects were compared to those obtained under insulin treatment. Blood metabolic parameters, *NO and ONOO- as well as protein carbonyl levels and cardiac hypertrophy were determined.
Results: Diabetic animals showed increased *NO levels and markedly increased ONOO- generation in the aorta, along with a significant hypertrophy and protein carbonylation in the cardiac tissue. Both AMNG and insulin treatment suppressed the levels of overproduced *NO or ONOO- in the vasculature, but only AMNG was able to prevent hypertrophic alterations and reduce protein carbonylation in the cardiac tissue.
Conclusions: Oxidative protein modification, together with cardiac hypertrophy and high generation of *NO and ONOO-, are important early events in the development of cardiovascular complications in diabetes. Aminoguanidine could prevent hypertrophy through inhibition of production of nonenzymatic glycation products rather than via inhibition of *NO production.
Copyright 2004 John Wiley & Sons, Ltd.