Pulmonary arterial hypertension (PAH) is a severe and progressive disease that leads to right heart failure. The pathogenesis of PAH is generally characterized by vasoconstriction, upregulated proliferation, migration, and pulmonary vascular remodeling in lung tissue. Recent studies using genetic analyses and experimental models have suggested that the hypercontraction of pulmonary arteries induced by Ca²⁺ signaling abnormality may be involved in the pathogenesis of PAH. We recently showed that the upregulation of mitochondrial Na⁺/Ca²⁺ exchanger (NCLX) contributes to the development of hypoxia-induced PAH, using NCLX genetically engineered mice. In the present study, we investigated the pathological mechanisms of NCLX in hypoxia-induced pulmonary hypertension. Pressure-induced arterial constriction was relaxed by specific NCLX inhibitor CGP-37157. Moreover, CGP-37157 suppressed hypoxia-induced migration of pulmonary arterial smooth muscle cells. These findings suggest that NCLX contributes to the development of pulmonary hypertension by promoting vascular hypercontraction and migration of pulmonary artery cells.