Growth hormone exerts acute vascular effects independent of systemic or muscle insulin-like growth factor I.
BACKGROUND
Endothelial dysfunction is common in patients with GH deficiency who are at increased risk for premature cardiovascular death. GH regulates vascular tone and reactivity in humans.


OBJECTIVE
Our objective was to explore the mechanisms underlying the GH's acute vascular effects. DESIGN AND STUDY SETTING: There were 10 healthy, lean and young, volunteers studied after an overnight fast. GH was infused systemically for 6 h at 0.06 microg/kg.min. Biopsy of the vastus lateralis muscle was done in seven subjects before and after GH infusion. Human aortic endothelial cells (HAECs) were incubated with GH in vitro.


RESULTS
GH infusion increased plasma GH to 32.9 +/- 1.5 ng/ml and forearm blood flow by 66% (P < 0.001). GH infusion did not significantly change plasma IGF-I concentrations, muscle IGF-I mRNA expression, and muscle Akt phosphorylation, suggesting a lack of IGF-I action in muscle. Because it was reported that GH exerts an acute vascular effect via a nitric oxide (NO)-dependent mechanism, we performed additional in vitro experiments using HAECs. HAECs express abundant GH receptors. Incubating HAECs with GH at 30 ng/ml for 3 or 6 h did not alter endothelial NO synthase (eNOS) protein content but time dependently increased the phosphorylation and activity of eNOS, thus demonstrating a direct effect of GH on endothelial cells.


CONCLUSIONS
GH exerts an acute vascular effect independent of both systemic and local IGF-I production, and this effect is likely via direct action on GH receptors and eNOS in the vascular endothelium.
Li
Guolian
G
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22908-1410, USA.
Del Rincon
Juan-Pablo
JP
Jahn
Linda A
LA
Wu
Yangsong
Y
Gaylinn
Bruce
B
Thorner
Michael O
MO
Liu
Zhenqi
Z
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001808:Blood Vessels / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000032:analysis; D012039:Regional Blood Flow / Q000187:drug effects
D001786:Blood Glucose; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt