2012, 2016), as well as cases refractory to iNO therapy, provided the basis for our search for more moderate ways to stimulate the endogenous NO response (EC eNOS>NO>SMC sGC>cGMP>Ca+2 > SMC relaxation) as a means to modulate PPHN. A screen for eNOS activators (serine‐1177 PO4) lead to the discovery of C1213, which was found to act as a functionally selective agonist on M3 receptors of pulmonary vascular endothelial cells. A summary of our main findings in endothelial cells and ex vivo and in vivo models of PPHN is presented in Figure 4. This evidence concerns the gene SGCB and persistent fetal circulation syndrome.