Context: Endothelial dysfunction is common in patients with GH deficiency who are at increased risk for premature cardiovascular death. Growth hormone (GH) regulates vascular tone and reactivity in humans.

Objective: To explore the mechanisms underlying the GH's acute vascular effects.

Design and Study Setting: Ten healthy, lean, and young volunteers were studied after an overnight fast. GH was infused systemically for 6 h at 0.06 µg/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 insulin-like growth factor I (IGF-I) concentrations, muscle IGF-I mRNA expression, and muscle Akt phosphorylation, suggesting a lack of IGF-I action in muscle. As it was reported that GH exerts acute vascular effect via a nitric oxide (NO)-dependent mechanism, we carried out additional in vitro experiments using HAECs. HAECs express abundant GH receptors. Incubating HAECs with GH at 30 ng/mL for 3 or 6 hrs 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: We conclude that GH exerts 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.