Abstract:

Objective   To explore the mechanism of fasudil improving MCT-induced PAH by studying the effect of fasudil on the expression of bone morphogenetic protein receptor (BMPR) in rat of monocrotaline (MCT)-induced pulmonary arterial hypertension. Methods   A total of 60 healthy Wistar rats of 4 weeks old were randomly divided into 6 groups: the early normal control group, the early model control group, the early fasudil group, the later normal control group, the later model control group, the later fasudil group. The ratios of arteriole wall thickness to vascular external diameter (WT%), and vascular area to total vascular area (WA%) were measured by a computerized image analyzer. The gene expression of BMPR1A and BMPR2 was determined by SYBGREEN RT-PCR. The protein expression of BMPR1A, BMPR2 and phosphorylated myosin phosphatase target protein-1(p-MYPT1)was determined by Western blotting. Results   Compared with the early/later normal control groups, the WT% and WA% increased significantly in the early/later model control groups(P＜0.05). After treated with fasudil, the WT% and WA% in the early/later model control groups was lower than that of the early/later normal control groups(P＜0.05). And in the later model control groups, the WT% and WA% obviously decreased compared with that of the early model control groups(P＜0.05). The gene and protein expression of BMPR1A, BMPR2 were lower in the early/later model control groups than that in the early/later normal control groups revealed by PCR and Western blotting(P＜0.05). After the treatment with fasudil, the WT% and WA% in the early/later fasudil groups increased significantly(P＜0.05). The expression of p-MYPT1 makeredly elevated in the early/later model control groups compared to that in the early/later normal control groups(P＜0.05). After treated wih fasudil, it decreased in the early/later fasudil groups(P＜0.05). Conclusion   Fasudil can inhibit and reverse the pulmonary artery smooth muscle proliferation of MCT-induced pulmonary artery remodeling in PAH in rats effectively by upregulating mRNA and protein expressions of BMPR.

Key words: Fasudil; Hypertension, pulmonary; Bone morphogenetic protein receptor; Pulmonary vascular remodeling