Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For example, NO is responsible for the bactericidal activities of macrophages, and in blood vessels it accounts for endothelium-derived relaxing factor activity. Recently, inhalation of NO gas was reported to improve the acute pulmonary arterial hypertension. Based on this knowledge, recombinant expression of endothelial nitric oxide synthase (eNOS) in lung may have profound effects on pulmonary vasomotor function and pulmonary arterial smooth muscle proliferation and platelet adhesion. On the basis of this concept, we evaluate the feasibility of gene therapy for chronic pulmonary arterial hypertension using hypoxia regulatable adenoviral vector coding eNOS cDNA.