Feedback vasodilation by endothelium-derived nitric oxide (NO) is under the regulation of globins. NIH Researchers discovered that not only the alpha globin but also the beta globin subunits of hemoglobin are expressed in the human artery wall, with beta globin interacting directly with endothelial nitric oxide synthase (eNOS). This discovery of tetrameric hemoglobin binding to eNOS has led inventors to develop novel mimetic peptides that disrupt the binding of beta globin to eNOS, diminishing the ability of hemoglobin to restrict NO release and thereby enhancing NO-mediated feedback vasodilation. These agents can be used to increase NO signaling from endothelial cells and thus inhibit, prevent, or reverse vasoconstriction.