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

Area of Science:

• Cardiology
• Endocrinology
• Physiology

Background:

• Cardiac hypertrophy (CH) is a significant cardiovascular response to stress.
• Androgens, like testosterone, may influence cardiac remodeling.
• The role of androgens in CH due to volume overload is not fully understood.

Purpose of the Study:

• To investigate the influence of androgens on cardiac hypertrophy (CH) induced by severe left ventricle (LV) volume overload (VO) in male rats.
• To determine if testosterone deficiency affects the development and molecular characteristics of CH.

Main Methods:

• Wistar rats underwent orchiectomy (Ocx) or sham operation (S), followed by induction of chronic aortic regurgitation (AR) or sham AR for 26 weeks.
• Evaluated body growth, LV dilation, systolic function (fractional shortening), cardiac gene expression, myocardial substrate utilization, and pJnk2 protein levels.

Main Results:

• Orchiectomy (Ocx) reduced overall body growth.
• Cardiac hypertrophy from AR was more pronounced in intact rats compared to Ocx rats (60% vs. 40%).
• LV dilation and systolic dysfunction were more severe in intact AR rats than in AROcx rats.
• Gene expression changes related to extracellular matrix remodeling and energy metabolism were more marked in intact AR rats.
• Testosterone deficiency attenuated CH, reduced LV dilation and systolic dysfunction, and normalized gene expression profiles.

Conclusions:

• Androgens, specifically testosterone, play a significant role in the development of cardiac hypertrophy and dysfunction caused by severe left ventricle volume overload.
• Testosterone deficiency appears to have a protective effect against the progression of cardiac hypertrophy and associated molecular changes.
• Androgen deprivation leads to less cardiac remodeling and a normalization of gene expression profiles in response to chronic volume overload.