NPPA and pulmonary arterial hypertension: However, chronic hypoxia can cause a decrease in intracellular ATP, which causes desensitization of ANP receptors (NPR-A, NPR-B, and NPR-C (Gaur et al., 2018) decreasing receptor activation, beside, another method for removal of ANP is through enzymatic degradation by membrane bound neural endopeptidase (NEP) the activation of this protein decreases the bioavailability of ANP, decreasing its biological action, as demonstrated by models of pulmonary hypertension due to chronic hypoxia (Misono et al., 2011).