However, in PAH, once synthesized, NO reacts with excessive ROS to form ONOO−, which leads to not only the oxidation of BH4 and sGC but also the loss or reduction of BH4 and sGC; these effects ultimately result in the disruption of the eNOS dimer and the insensitivity of sGC to NO [36]. Here, NOS3 is linked to pulmonary arterial hypertension.