Influence of different doses of retinoic acid on cardiac remodeling

Objective: The role of retinoic acid in promoting postnatal heart alterations is still unclear. The aim of this study was to evaluate whether the cardiac alterations caused by all-trans- retinoic acid (ATRA) in normal adult rat hearts are physiologic or pathologic and if these alterations are dose-dependent. Methods: Rats were allocated into a control group that received a diet without ATRA (n = 16), a group that received 0.3 mg of ATRA/kg of diet (n = 17), a group that received a diet containing 10 mg of ATRA/kg (n = 18), or a group that received 50 mg of ATRA/kg in the diet (n = 18). After 4 wk, the animals were evaluated echocardiographically, morphologically, and biochemically. Results: The 50-mg ATRA group presented cardiac hypertrophy with maintenance of cardiac geometry and increased systolic function, whereas diastolic function was similar to that of the control group. In addition, progressive increases in the ATRA dose resulted in gradual augmentations of left atrial diameter, left ventricular diastolic and systolic diameters, left ventricular mass index, cardiac output, cardiac index, and aortic velocity. The ATRA did not produce alterations in interferon-gamma and tumor necrosis factor-alpha cardiac levels, interstitial collagen volume fraction, or the intensity and localization of connexin-43. In addition, no alteration was observed in beta-hydroxyacyl coenzyme A dehydrogenase, lactate dehydrogenase, or citrate synthase, suggesting that cardiac energetic metabolism was preserved with ATRA. Conclusion: These results suggest that ATRA produced dose-dependent effects and cardiac remodeling that is more compatible with a physiologic response. (C) 2011 Elsevier Inc. All rights reserved.