[Effects of 764-3 on collagen deposition in hypertensive pulmonary arteries in hypoxic rats].

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.