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

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.

journal_name

Br J Pharmacol

authors

Wu MS,Liang JT,Lin YD,Wu ET,Tseng YZ,Chang KC

doi

10.1038/bjp.2008.119

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

758-64

issue

4

eissn

0007-1188

issn

1476-5381

pii

bjp2008119

journal_volume

154

pub_type

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