Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling

Prostacyclin (PGI(2)) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction follo wing ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI(2) receptor (PGI-R) expression in the remo deled pulmonary arterial smooth muscle, we hypothesized that pulmonary vasc ular 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 pr essure and lung histology were assessed. The PGI-R KO mice developed more s evere pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI(2) and its receptor play an important role in the regulation of hypoxia-induced p ulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.