Objective: To investigate the changes of collagen deposition in pulmonary arteries in chronic hypobaric hypoxic rats and the roles of 764-3.
Methods: Wistar rats were divided into 10 groups. The hypoxic (50.7 kPa) rats were treated with 764-3 (20 mg/kg, once daily) and beta-aminopropionitrile (BAPN, 150 mg/kg, twice daily), respectively. At the end of treatment, the hemodynamic morphological and chemical parameters were measured.
Results: Comparing with the normals, hydroxyproline (HYP) content of extrapulmonary artery (EPA) increased obviously in hypoxic rats, the smooth muscle cells (SMC) in the media of muscular intra-acinar pulmonary artery showed hypertrophy with change in phenotype, and a striking increment of collagen accumulation (P < 0.001); 764-3 could reduce HYP content of EPA (P < 0.05-0.001), and most of SMC in the media became thin and elongated with reversion of change of SMC phenotype, and collagen accumulation was reduced (P < 0.001). In addition, BAPN was more effective than 764-3 (P < 0.05).
Conclusions: Excessive collagen accumulation in pulmonary arteries plays an important role in the maintenance of hypoxic pulmonary hypertension. 764-3 can partially inhibit collagen deposition in pulmonary arteries, attenuate hypoxic pulmonary hypertension, and has a moderate influence on collagen deposition in compared with BAPN.