AMINOGUANIDINE HAS AN ANTI-ATHEROGENIC EFFECT IN THE CHOLESTEROL-FED RABBIT

Advanced glycosylation endproducts (AGEs) which result from the non-en zymatic interaction of proteins and glucose are implicated in the vasc ulopathy of diabetes and aging. Since aminoguanidine (A) inhibits the accumulation of AGEs, we explored its effects on the development of at herosclerosis. Male New Zealand white cross rabbits fed a high cholest erol (1%) diet were randomized to control (C) or increasing doses of A treatment (25, 50 and 100 mg/kg A body weight). The animals were sacr ificed after 12 weeks. Sudan IV was used to stain the lipid containing plaques of the aortic arch, thoracic and abdominal aorta and the surf ace area occupied by atheroma was assessed. Increasing doses of A trea tment were associated with reduction in plaque formation in the aorta. At a dose of 100 mg/kg A, there was a 30, 49 and 48% reduction in pla que formation in the aortic arch, thoracic and abdominal aorta, respec tively. There was a correlation between AGE levels and the degree of a theroma in these cholesterol fed rabbits (control, r = 0.75, P < 0.01; 100 mg/kg A, r = 0.59, P = 0.02). These data suggest that advanced gl ycation may participate in atherogenesis and raise the possibility tha t inhibitors of advanced glycation may retard this process. (C) 1998 E lsevier Science Ireland Ltd.