In mesenteric arteries, Ca2+ entry through the TRPV4 channel at the myoendothelial projections (MEPs) determines vasodilation via activation of nearby small (SK) and intermediate (IK) conductance Ca2+-activated K+ channels. Co-localization of endothelial nitric oxide synthase (eNOS) with hemoglobin alpha (Hbα), a nitric oxide (NO) scavenging protein, prevents TRPV4-eNOS signaling. On the contrary, in pulmonary arteries, IK/SK channels and Hbα do not localize at MEPs. Therefore, Ca2+ influx via TRPV4 channel activates eNOS causing NO-dependent vasodilation. EC, endothelial cell.