Effects of Testosterone on Obesity-Related Cardiac Hypertrophy and Fibrosis

Wilson, Ana Kaye. Effects of testosterone on obesity-related cardiac hypertrophy and fibrosis. Master of Science (Integrative Physiology), August 2009, 71 pp, 3 tables, 6 figures. Both testosterone and obesity are known to increase renin-angiotensin system activity, leading to cardiovascular dysfunction. This study determined the interactive effects of obesity and testosterone on left ventricular hypertrophy and cardiac fibrotic factors. Male New Zealand White rabbits were fed a lean or 10% added fat diet. After 12 weeks, fat-fed rabbits exhibited increased left ventricular weight (6.05±0.16 vs. 4.75±0.10 g, respectively, p≤0.05) and cardiomyocyte cross-sectional area compared to lean rabbits (372.3±19.0 vs. 305.0±13.4μm2, respectively; p≤0.01). These effects were attenuated by both castration and treatment with the angiotensin type 1 receptor blocker, losartan. Obese rabbits did not exhibit increased myocardial collagen as expected. However, castration and losartan treatment increased matrix metalloproteinase-2 (MMP-2) activity in obese rabbits. Despite the effects of castration hypertrophy and MMP-2 activity, castration did not attenuate plasma renin activity of aldosterone. These data suggest that testosterone contributes to obesity-related left ventricular hypertrophy and decreases collagen degradation, independent of renin activity.