Objective: To investigate the effects of chronic hypoxic hypercapnia and ligustrazine on expression of endothelin-1 (ET-1) mRNA and the ultrastructure of pulmonary arterioles in rats.
Methods: Thirty rats were randomly divided into three groups: control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + ligustrazine (lig.) group (C). ET-1 mRNA was observed in arterioles from rats by the technique of in situ hybridization. The average value of integral light density (LD) of ET-1 mRNA in pulmonary arterioles was detected by an image analysor and the relative content of ET-1 mRNA was calculated.
Results: (1) mPAP was significantly higher in rats of B group than that of A group (P < 0.01) and it was much lower in rats of C group than that of B group (P < 0.01). Differences of mCAP were not significant in three groups (P > 0.05); plasma ET-1 concentration was significantly higher in rats of B group than that of A group (P < 0.01), plasma ET-1 concentration was significantly lower in rats of C group than that of B group (P < 0.01); (2) Light microscopy showed that WA/TA (vessel wall area/total area) and SMC (the density of medial smooth muscle cells) were significantly higher in rats of B group than those of A group (P < 0.01). WA/TA and SMC were significantly lower in rats of C group than those of B group (P < 0.01). Electron microscopy showed proliferation of medial smooth muscle cells and collageous fibers of pulmonary arterioles in rats of B group, and ligustrazine could reverse the changes mentioned above; (3) Hybridization in situ showed that LD of ET-1 mRNA in pulmonary arterioles was significantly higher in rats of B group than that of A group (P < 0.01); LD of ET-1 mRNA in pulmonary arterioles was significantly lower in rats of C group than that of B group (P < 0.01).
Conclusions: Increase of expression of ET-1 mRNA in pulmonary arterioles contributes to the development of pulmonary hypertension and structural remodeling of pulmonary arteries in chronic hypoxic hypercapnic rats. Ligustrazine can inhibit pulmonary hypertension by decreasing the expression of ET-1 mRNA in pulmonary arterioles.