NO, an endothelium-derived relaxing factor, suppressed hypoxia-induced ET-1 expression and synthesis.237 This implies that hypoxia disrupts the ET-1/NO balance, leading to defective NO synthesis and augmented ET-1 production, which are causally linked to exaggerated pulmonary hypertension and HAPE pathogenesis. The gene discussed is EDN1; the disease is pulmonary arterial hypertension.