Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling

Prostacyclin (PGI₂) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction following ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI₂ receptor (PGI-R) expression in the remodeled pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of 17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung histology were assessed. The PGI-R KO mice developed more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI₂ and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.