Testosterone deficiency reduces cardiac hypertrophy in a rat model of severe volume overload.

The aim of the study was to characterize if the development of cardiac hypertrophy (CH) caused by severe left ventricle (LV) volume overload (VO) from chronic aortic valve regurgitation (AR) in male rats was influenced by androgens. We studied Wistar rats with/without orchiectomy (Ocx) either sham-operated (S) or with severe AR for 26 weeks. Loss of testosterone induced by Ocx decreased general body growth. Cardiac hypertrophy resulting from AR was relatively more important in intact (non-Ocx) animals than in Ocx ones compared to their respective S group (60% vs. 40%; P = 0.019). The intact AR group had more LV dilation, end-diastolic LV diameter being increased by 37% over S group and by 17% in AROcx rats (P < 0.0001). Fractional shortening (an index of systolic function) decreased only by 15% in AROcx compared to 26% for intact AR animals (P = 0.029). Changes in LV gene expression resulting from CH were more marked in intact rats than in AROcx animals, especially for genes linked to extracellular matrix remodeling and energy metabolism. The ratio of hydroxyacyl-Coenzyme A dehydrogenase activity over hexokinase activity, an index of the shift of myocardial substrate use toward glucose from the preferred fatty acids, was significantly decreased in the AR group but not in AROcx. Finally, pJnk2 LV protein content was more abundant in AR than in AROcx rats, indicating decreased activation of this stress pathway in the absence of androgens. In summary, testosterone deficiency in rats with severe LV VO resulted in less CH and a normalization of the LV gene expression profile.