Constitutive and inducible nitric oxide synthase: role in angiogenesis

Since the initial report of nitric oxide (NO) activity, enormous progress has been made over the last two decades in the field of NO research. Whereas most physiological responses triggered by moderate concentrations of NO are mediated by soluble guanylate cyclase activation and the subsequent production of cyclic GMP as the major signaling messenger, recent studies have provided evidence of alternative signaling pathways triggered by high concentrations of NO. These signals operate in part through redox-sensitive regulation of transcription factors, gene expression, transcription, cellular activation, proliferation, and cell death. Numerous results converge to indicate a role for NO in physiological and pathological angiogenesis. Experimental data indicate that NO synthase, depending on the isoforms, the timing, and the degree of activation, may display contradictory effects, expressed during both physiological and pathological angiogenesis. The dual personality of NO will be reviewed in the context of the angiogenesis process.