Context and Objective: Impaired nitric oxide (NO) bioavailability and low levels of circulating endothelial progenitor cells (EPC) are correlated to an increased risk for development of cardiovascular diseases. We investigated whether improved systemic NO bioavailability and increased levels of EPC after growth hormone treatment are related and mediated by the insulin-like growth factor-1 (IGF-1).

Design, Patients and Results: Healthy middle aged volunteers (n = 16) were treated for 10 days with recombinant human growth hormone (GH). Before and after GH treatment we analyzed markers of NO bioavailability and EPC levels. GH treatment was responded by significant increases in plasma IGF-1 levels. Urinary cGMP levels were increased and diastolic blood pressure reduced after GH treatment (P < 0.05). Likewise, plasma nitrate and nitrite (NOx) levels were increased, whereas the NO synthase inhibitor ADMA was reduced. Correspondingly, IGF-1 treatment increased expression of the ADMA metabolizing enzyme DDAH1 and DDAH2 in cultured human endothelial cells. IGF-1 levels correlated with cGMP concentrations (r = 0.51; P < 0.05). EPC numbers were increased after GH treatment and correlated with markers for NO bioavailability. These findings were also observed in mice treated with GH for 7 days. GH treatment additionally increased aortic eNOS expression of mice. Importantly, blocking of the IGF-1 receptor in vivo abolished the GH-mediated effects on markers of increased NO bioavailability.

Conclusions: Growth hormone treatment induced markers of increased NO bioavailability and enhanced circulating EPC numbers in healthy volunteers. Animal data demonstrate increased NO availability to be mediated via an increase in IGF-1 plasma levels. Thus, GH treatment enhances systemic NO bioavailability via IGF-1 and may be beneficial in certain cardiovascular diseases.