The subject invention provides materials and methods useful in regulating blood flow. In a preferred embodiment, the subject invention provides peptides that are able to enhance nitric oxide (NO) activity and/or elevate cellular guanosine monophosphate (cGMP). Through these mechanisms, the subject invention can be used advantageously to effect vasorelaxation, thereby providing therapeutic benefit in a variety of contexts. In a specific embodiment the subject invention provides novel peptides that have been found to enhance the activity of endothelial cell nitric oxide synthase (eNOS). These peptides have also been found to reduce the cGMP-specific phosphodiesterase activity.