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 (50 mg kg −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, E max 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. British Journal of Pharmacology (2008) 154 , 758–764; doi: 10.1038/bjp.2008.119 ; published online 31 March 2008