Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.
OBJECTIVE
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)).


METHODS
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.


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
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.
Wu
M-S
MS
Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Liang
J-T
JT
Lin
Y-D
YD
Wu
E-T
ET
Tseng
Y-Z
YZ
Chang
K-C
KC
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000494:pharmacology*; D006334:Heart Function Tests; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009536:Niacinamide; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D016277:Ventricular Function, Left / Q000187:drug effects
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D009536:Niacinamide; D013311:Streptozocin; C004479:pimagedine