Aminoguanidine prevents arterial stiffening and cardiac hypertrophy in streptozotocin‐induced diabetes in rats

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg(-1) STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg(-1)) and compared with the age-matched untreated diabetic controls. After exposure to AG, the STZ-diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (tau), from 20.4+/-0.6 to 24.7+/-0.5 ms (P<0.05) and a decrease in wave reflection factor (R(f)), from 0.78+/-0.04 to 0.53+/-0.02 (P<0.05). The decreased R(f) associated with the increased tau suggest that AG may retard the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, the diminished ratio of left ventricular weight to body weight suggests that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Glycation-derived modification on aortic collagen was also found to be enhanced in rats with diabetes (+65.3%, P<0.05) and the advanced glycation process was retarded by AG treatment. We conclude that long-term administration of AG to the STZ-treated rats imparts significant protection against the diabetes-derived deterioration in vascular dynamics, at least partly through inhibition of the AGEs accumulation on collagen in the arterial wall.