Effect of prenatal tetrandrine therapy on pulmonary vascular structural remodeling in the nitrofen-induced CDH rat model.

OBJECTIVE

To examine the effects of prenatal tetrandrine (Tet) therapy on pulmonary arterial structural remodeling in nitrofen-induced congenital diaphragmatic hernia (CDH).

METHODS

CDH was induced in fetal rats by maternal administration of 100 mg nitrofen by gavage on day 9.5 of gestation (term, day 22). Control animals received olive oil (OO). Tet (24 mg/kg per day) or normal saline (NS) was given by gavage every day from 16 to 20 days of gestation, and fetuses were delivered by caesarean section on day 21.5. Lung sections from 3 fetuses in each group were studied. The number of vessels were calculated, the external diameter (ED), medial wall thickness (MT), percent of medial wall thickness, and wall structure were evaluated by image analysis software.

RESULTS

In the pre-acinar arteries, CDH-NS pups had a significantly increased %MT compared with the OO-NS group (P < 0.05), while CDH-Tet animals had a reduced %MT compared with the CDH-NS rats (P < 0.05). Similar results were seen in the intra-acinar level. Significant differences were observed between CDH-NS animals and OO-NS controls in the percentage of muscularized intra-acinar blood vessels (P < 0.001). Tet-treated CDH pups had a reduced percentage of muscularized intra-acinar arteries compared with CDH-NS animals.

CONCLUSIONS

Medial hypertrophy is present in both the pre-acinar and intra-acinar arteries in the nitrofen-induced CDH rat model. Tet treatment inhibits medial hypertrophy and reduces the percentage of muscularized intra-acinar vessels. Prenatal Tet therapy may be efficacious in reducing the risk of PH in human newborns with CDH.