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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:28-35 (2006)
© 2006 The Gerontological Society of America

Growth Hormone Replacement Attenuates Diastolic Dysfunction and Cardiac Angiotensin II Expression in Senescent Rats

Leanne Groban, Nathan A. Pailes, Colleen D. L. Bennett, Christy S. Carter, Mark C. Chappell, Dalane W. Kitzman and William E. Sonntag

Departments of Anesthesiology, Physiology and Pharmacology, Hypertension & Vascular Disease Center, and the Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Address correspondence to Leanne Groban, MD, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009. E-mail: lgroban{at}wfubmc.edu

We tested the hypothesis that long-term growth hormone (GH) replacement in aged rats would preserve diastolic function and attenuate left ventricular remodeling associated with normal aging. Male Brown Norway x F344 rats were randomized to receive twice daily injections of porcine GH (200 µg/injection, subcutaneous) or saline from 24 to 30 months of age. Adult rats (6- to 9-months old) received saline injections throughout the study. Thirty-month-old, saline-treated rats exhibited low levels of insulin-like growth factor 1 (IGF-1), impaired diastolic left ventricular filling (Doppler), increased cardiac angiotensin II (Ang II), reduced plasma Ang II, and increased cardiac collagen. GH administration in old rats restored IGF-1 and diastolic indices to values comparable to those of adults. These effects were associated with reduced cardiac Ang II and attenuations in cardiac collagen. Age-related decreases in GH and IGF-1 may contribute to the decline in diastolic function of aging, in part through alterations in renin–angiotensin system-mediated ventricular remodeling.




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