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- Title
Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.
- Authors
Wu, M.-S.; Liang, J.-T.; Lin, Y.-D.; Wu, E.-T.; Tseng, Y.-Z.; Chang, K.-C.
- Abstract
<bold>Background and Purpose: </bold>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)).<bold>Experimental Approach: </bold>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.<bold>Key Results: </bold>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.<bold>Conclusions and Implications: </bold>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.
- Subjects
DIABETES; STREPTOZOTOCIN; NICOTINAMIDE; MYOCARDIUM; PHARMACOLOGY; DIABETES complications; BIOLOGICAL models; LEFT heart ventricle; RESEARCH; ANIMAL experimentation; RESEARCH methodology; CARDIAC contraction; ORGANIC compounds; MEDICAL cooperation; EVALUATION research; TYPE 2 diabetes; RATS; VITAMIN B complex; COMPARATIVE studies; HEART function tests; HEART physiology; ENZYME inhibitors; PHARMACODYNAMICS; DISEASE complications
- Publication
British Journal of Pharmacology, 2008, Vol 154, Issue 4, p758
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.119