Nitric oxide (NO) increases expression of vascular endothelium growth factor (VEGF) in cultured cells

VEGF is an endothelial cell-specific mitogen which stimulates angiogenesis in embryonic and adult tissues. Its expression in numerous cell types is upregulated by various signals including hypoxia and hypoglycemia. Because NO is an important vasoactive factor with gene regulatory activity, we have examined its effect on VEGF expression. Northern analysis showed that the NO donors, S-nitroso-N-acetyl-penicillamine (SNAP) and spermine-NO (0.01-1.0 mM), caused concentration- and time-dependent increases of VEGF mRNA in mouse fetal lung mesenchymal cells (MFLM). SNAP also increased VEGF in adult mouse lung epithelial cells and in both growing and quiescent bovine pulmonary artery smooth muscle cells. VEGF upregulation in MFLM was not mediated by cGMP, because the response to SNAP was neither potentiated by zaprinast nor mimicked by 8-br-cGMP. Actinomycin D (5 μg/ml)-chase experiments indicated that the upregulation was due at least partly to increased VEGF mRNA stability. These results raise the possibility that NO plays a role in angiogenesis hy stimul.iting VEGF expression.