IGF-1 is produced by vascular cells in response to injury; it promotes vascular smooth muscle cell hypertrophy and proliferation, and increases extracellular matrix production. NO regulates vascular tone and inhibits smooth muscle cell proliferation as well as total protein and collagen synthesis. NO synthesis is regulated by several peptide growth factors. We hypothesized that IGF-1 reduces the production of NO in cultured PASMC. To test this hypothesis, PASMC were isolated from the main pulmonary artery of newborn piglets and grown to confluence in 24 well plates in Eagle MEM + 10% fetal calf serum before being incubated in serum-free media (SFM) for 24 hours. Media was then replaced with fresh SFM and cells were exposed to 500 U/ml of tumor necrosis factor alpha (TNFα) and 20 ug/ml of lipopolysaccharide (LPS) to stimulate NO production. At the same time, IGF-1 was added to the wells at 3 different concentrations (10, 30, and 50 ng/ml). Cells without TNFα, LPS or IGF-1 were used as controls. After 48 hours, NO production was assessed by cumulative nitrate levels measured by colorimetry. Cell viability was confirmed by trypan blue exclusion. The experiment was repeated 3 times and the results analyzed by ANOVA followed by the Bonferroni test. TNFα and LPS increased nitrate levels by 39±3%. IGF-1 inhibited the accumulation of nitrate in SFM in a concentration-dependent manner. Our results indicate that IGF-1 inhibits the cytokine-induced production of NO by neonatal PASMC. We speculate that IGF-1 may be a modulator of NO production at sites of pulmonary vascular injury.Figure

figure 1

Figure 1