Acute Vascular Effects of GH Appear to be Independent of Both Local and Systemic IGF-I Production
Growth hormone (GH) has been shown to regulate vascular tone and reactivity in humans, but it is unclear whether this action is a result of a direct stimulatory effect of GH or if it is dependent on systemic and local insulin-like growth factor (IGF)-I production. In this study, Li et al evaluated the mechanisms underlying the acute vascular effects of GH. Ten healthy lean young volunteers (20 to 27 years of age; 7 male and 3 females) were studied after an overnight fast. GH was infused for 6 hours at 0.06 mcg/kg/minute and a biopsy of the vastus lateralis muscle was obtained in 7 of these subjects before and after infusion for analysis of IGF-I mRNA and Akt phosphorilation. Blood was obtained serially every 10 minutes during the infusion for GH, IGF-I, insulin and glucose assessments. GH infusion increased plasma GH and forearm blood flow by 66% (p<0.001), but did not change plasma IGF-I concentrations, muscle IGF-I mRNA expression and muscle Akt phosphorylation, therefore suggesting a lack of IGF-I action in muscle. Additionally, human aortic endothelial cells (HAECs) were incubated with GH in vitro for 3 to 6 hours did not alter endothelial nitric oxide synthase (eNOS) protein content, but increased time dependently the phosphorylation and activity of eNOS. This study demonstrated that GH exerts an acute vascular effect, independent of both systemic and local IGF-I production and that this effect probably occurs via direct action on GH receptors and eNOS in the vascular endothelium.
Endothelial dysfunction appears to explain much of the increased cardiovascular risk of GH deficiency. GH seems to play an important role in the regulation of peripheral vascular resistance and vascular reactivity and these effects appear to be mediated by the activation of the nitric oxide pathway. GH deficiency is associated with decreased systemic nitric oxide formation and decreased forearm release of nitrite and cyclic GMP during acetylcholine stimulation, as well as a decreased peak hyperemic response to ischemia, which reverts to normal during GH replacement. Significant endothelial dysfunction as determined by an impaired endothelium-dependent brachial artery dilatory response to occlusion ischemia and by abnormalities of several biochemical markers of endothelial cell activation have been reported in adolescents and adults with GHD.1,2It is, however, not clear whether these effects are a result of a direct effect of GH on the vascular endothelium or whether they are dependent on systemic and local IGF-I production. In this study, Li et al demonstrated how GH infusion increased plasma GH and forearm blood flow. This effect occurred without a significant change in plasma IGF-I concentrations, muscle IGF-I mRNA expression or muscle Akt phosphorylation, suggesting a lack of IGF action in muscle. In addition the incubation of HAECs with GH time dependently increased the phosphorylation and activity of eNOs, This study seems to indicate that the acute vasodilatory effect of GH is exerted independent of IGF-I, very possibly through GH receptor mediated eNOS activation.
Roberto Lanes, MD
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