Aminoguanidine Prevents the Impairment of Cardiac Pumping Mechanics in Rats with Streptozotocin and Nicotinamide-Induced Type 2 Diabetes

Background and purpose: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E-max) and theoretical maximum flow (Q(max)). Experimental approach: After induction of type 2 diabetes, rats received daily injections of AG (50mgkg(-1), i. p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E- max and Q(max), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance. Key results: Both type 2 diabetes and AG affected E-max and Q(max), and there was an interaction between diabetes and AG for these two variables. The E- max and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA- induced diabetic rats were treated with AG. Conclusions and implications: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes