Low-dose growth hormone is cardioprotective in uremia.
Growth hormone (GH) is required to maintain normal cardiac structure and function and has a positive effect on cardiac remodeling in experimental and possibly human disease. Cardiac resistance to GH develops in the uremic state, perhaps predisposing to the characteristic cardiomyopathy associated with uremia. It was hypothesized that administration of low-dosage GH may have a salutary effect on the cardiac remodeling process in uremia, but because high levels of GH have adverse cardiac effects, administration of high-dosage GH may worsen uremic cardiomyopathy. In rats with chronic renal failure, quantitative cardiac morphology revealed a decrease in total capillary length and capillary length density and an increase in mean intercapillary distance and fibroblast volume density evident. Low-dosage GH prevented these changes. Collagen and TGF-beta immunostaining, increased in chronic renal failure, were also reduced by GH, suggesting a mechanism for its salutary action. Low-dosage GH also prevented thickening of the carotid artery but did not affect aortic pathology. In contrast, high-dosage GH worsened several of these variables. These results suggest that low-dosage GH may benefit the heart and possibly the carotid arteries in chronic renal failure.
Rabkin
Ralph
R
Department of Medicine, Stanford University and Research Service, Veterans Administration Health Care System, Palo Alto, California 94304, USA. rabkin@stanford.edu
Awwad
Ibrahim
I
Chen
Yu
Y
Ashley
Euan A
EA
Sun
Difei
D
Sood
Sumita
S
Clusin
William
W
Heidenreich
Paul
P
Piecha
Grzegorz
G
Gross
Marie-Luise
ML
D000818:Animals; D001158:Arteries / Q000473:pathology; D001794:Blood Pressure; D001835:Body Weight; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015870:Gene Expression; D013006:Growth Hormone / Q000008:administration & dosage*; D006400:Hematocrit; D006439:Hemodynamics; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000097:blood / Q000150:complications* / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects*
D013006:Growth Hormone