Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes
Journal
British Journal of Pharmacology
Journal Volume
154
Journal Issue
4
Pages
758-764
Date Issued
2008
Author(s)
Abstract
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. ? 2008 Nature Publishing Group All rights reserved.
SDGs
Other Subjects
advanced glycation end product; aminoguanidine; nicotinamide; streptozocin; animal experiment; animal model; aorta flow; arterial stiffness; artery compliance; article; controlled study; drug effect; heart afterload; heart left ventricle pressure; heart ventricle hypertrophy; male; non insulin dependent diabetes mellitus; nonhuman; oxidative stress; priority journal; rat; statistical analysis; streptozocin diabetes; systemic vascular resistance; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Enzyme Inhibitors; Glycosylation End Products, Advanced; Guanidines; Heart Function Tests; Male; Myocardial Contraction; Niacinamide; Rats; Rats, Wistar; Streptozocin; Ventricular Function, Left
Type
journal article