CONTEXT: 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.
CONTEXT: 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.
Authors: Carmen Gonzalez; Hector Rosas-Hernandez; Brenda Jurado-Manzano; Manuel Alejandro Ramirez-Lee; Samuel Salazar-Garcia; Pedro Pablo Martinez-Cuevas; Aída Jimena Velarde-Salcedo; Humberto Morales-Loredo; Ricardo Espinosa-Tanguma; Syed F Ali; Rafael Rubio Journal: Acta Pharmacol Sin Date: 2015-04-20 Impact factor: 6.150
Authors: Kurt A Mossberg; William J Durham; Dennis J Zgaljardic; Charles R Gilkison; Christopher P Danesi; Melinda Sheffield-Moore; Brent E Masel; Randall J Urban Journal: J Neurotrauma Date: 2016-10-13 Impact factor: 5.269
Authors: Kevin S Heffernan; Christopher A Fahs; Sushant M Ranadive; Eshan A Patvardhan Journal: J Cardiovasc Pharmacol Ther Date: 2010-01-06 Impact factor: 2.457