Aminoguanidine prevents age-related deterioration in left ventricular-arterial coupling in Fisher 344 rats

Abstract

1. In recent studies, aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that can prevent the age-related aortic stiffening and cardiac hypertrophy. The aim of this study was to determine whether AG had effects on the left ventricular (LV)-arterial coupling in aged Fisher 344 rats in terms of the ventricular and arterial chamber properties. 2. Normotensive rats were treated from 18 to 24 months with AG (1 gl -1 in drinking water) and compared with a control group. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E es) and effective arterial volume elastance (E a), respectively. The optimal afterload (Q load) determined by the ratio of E a to E es was used to measure the efficiency of mechanical energy transferred from the left ventricle to the arterial system. 3. In comparison with the 6-month-old rats, the 24-month-old animals had decreased E es, at 567.4±26.7 vs 639.0±20.7 mmHg ml -1, decreased E a, at 411.5±18.6 vs 577.9±15.7 mmHg ml -1, and decreased Q load, at 0.9428±0.0024 vs 0.9962±0.0014. 4. Treatment with AG for 6 months did not significantly affect E es; however, when normalized to LV weight (i.e., E esn = E es/LV weight), E esn showed a significant rise of 22.8%, suggesting that AG may retard the aging process on the intrinsic contractility of the left ventricle. On the other hand, the decrease in E a in aging rats was prevented by AG, as reflected in the increase of 19.7% in this variable (P<0.05). The 24-month-old treated rats also exhibited a significant rise of 21.6% in E a/E es, causing an increase of 5.2% in Q load (P<0.05). 5. We conclude that in healthy older Fisher 344 rats without diabetes, long-term treatment with AG may improve both the arterial and ventricular function and optimize the matching condition for the left ventricular-arterial coupling.