Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats.
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 microg/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.
Groban
Leanne
L
Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA. lgroban@wfubmc.edu
Pailes
Nathan A
NA
Bennett
Colleen D L
CD
Carter
Christy S
CS
Chappell
Mark C
MC
Kitzman
Dalane W
DW
Sonntag
William E
WE
D000375:Aging / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D003971:Diastole / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
D000804:Angiotensin II; D013006:Growth Hormone