Submitted on April 15, 2005
Accepted on August 2, 2005
Comparative Effects of Dehydroepiandrosterone Sulfate on Ventricular Diastolic Function withYoung and Aged Female Mice
Cory M Alwardt1, Qianli Yu2, Heddwen L Brooks3, Matthew R McReynolds3, Randy Vazquez4, Ronald Ross Watson4, and Douglas F Larson2*
1 Sarver Heart Center, The University of Arizona, Tucson, AZ, USA; Department of Physiology, The University of Arizona, Tucson, AZ, USA
2 Sarver Heart Center, The University of Arizona, Tucson, AZ, USA; Department of Medical Pharmacology, The University of Arizona, Tucson, AZ, USA
3 Department of Physiology, The University of Arizona, Tucson, AZ, USA
4 Department of Health Promotions Sciences, The University of Arizona, Tucson, AZ, USA
* To whom correspondence should be addressed. E-mail: dflarson{at}u.arizona.edu.
The adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S)) have been extensively studied due to potential anti-aging effects. Associated with aging. DHEA levels decline in humans while other adrenal hormones remain unchanged, suggesting that DHEA may be important in the aging process. However, the effect of DHEA(S) supplementation on cardiac function in the aged has not been investigated. Therefore, we administered to young and old female mice a 60-day treatment with exogenous DHEA(S) at a dose of 0.1 mg/mL in the drinking water and compared the effects on left ventricular diastolic function and the myocardial extracellular matrix composition. The left ventricular stiffness (
) was 0.30 ± 0.06 mmHg/µl in the older control mice, compared with 0.17 ± 0.02 mmHg/µl young control mice. Treatment with DHEA(S) decreased to 0.12 ± 0.03 mmHg/µl in the older mice and increased to 0.27 ± 0.04 mmHg/µl in young mice. The mechanism for the DHEA(S)-induced changes in diastolic function appeared to be associated with altered MMP activity and the percentage of collagen crosslinking. We conclude that exogenous DHEA(S) supplementation is capable of reversing the left ventricular stiffness and fibrosis that accompanies aging, with a paradoxical increased ventricular stiffness in young mice.
