NOS2 and pulmonary arterial hypertension: This upregulation is driven by the activation of the AP-1 pathway and an independent NF-κB pathway, which subsequently enhances the expression of iNOS through activation of the ERK1/2 and JNK pathways.381 The medium derived from periostin-induced RVFs inhibits L-type Ca2+ channel activity in CMs through NO production.381 This implies that NO generation involving the MAPK pathway may contribute to contractile dysfunction in RV failure associated with PAH.