DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2005; 21: 189–196. Published online 27 July 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/dmrr.501 Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats Kriszti´ an Stadler 1 * Veronika Jenei 1 Anik´ o Somogyi 2 Judit Jakus 1 1 Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary 2 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary *Correspondence to: Dr Kriszti´ an Stadler, Institute of Chemistry, Chemical Research Center of the Hungarian Academy of Sciences, 1525 Budapest, P.O. Box 17, Hungary. E-mail: krisz@chemres.hu Received: 20 January 2004 Revised: 26 April 2004 Accepted: 11 May 2004 Abstract Background The study focused on investigating the effect of aminoguani- dine 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, ž NO and ONOO − as well as protein carbonyl levels and cardiac hypertrophy were determined. Results Diabetic animals showed increased ž 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 ž 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 hyper- trophy and high generation of ž 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 ž NO production. Copyright  2005 John Wiley & Sons, Ltd. Keywords aminoguanidine; insulin; nitric oxide; diabetes; cardiac hypertrophy; EPR spectroscopy Introduction Diabetes mellitus is one of the chronic metabolic diseases, which involves redox imbalance and increased oxidative stress [1]. Epidemiological studies show that high mortality in diabetic patients can be explained by factors other than hyperglycemia, notably an increased risk of vascular diseases like atherosclerosis, cardiac hypertrophy, and other cardiovascular diseases. Elevated levels of free radicals, especially those of reactive oxygen species (ROS) [2], are suggested to play a crucial role in the development of the disease and its late complications [3–6] through nonenzymatic gly- cation of proteins, formation of advanced glycation end products (AGEs) [7], and other oxidative modifications. Nitric oxide ( ž NO), which is an important radical in the physiology of vasodilatation and pathophysiology of cardiovascular diseases, has also been intensively studied in diabetes [8–10]. It plays an important yet controversial role in diabetes melli- tus, in endothelium-dependent relaxation of the microvasculature, and in Copyright  2005 John Wiley & Sons, Ltd.