Sildenafil improves the function of endothelial cells in patients suffering from congenital heart disease with pulmonary hypertension.

Aim of this study was to investigate the potential effects of sildenafil on the function of endothelial cells from patients with congenital heart disease with pulmonary hypertension (CHDPH). Patients who are diagnosed as CHD with PH (n=30) or without PH (n=30), and 30 healthy persons (control) were enrolled in this study. The 30 CHDPH cases were separated into two groups, one was given aspirin while the other received aspirin and sildenafil. An ELISA assay was used to detect the biological indexes for endothelial cells. Furthermore, 24 male New Zealand white rabbits were used to construct the CHDPH model. The signal pathway-related protein expression was analyzed using RT-PCR and western blotting. Compared to that in healthy people, levels for flowmediated dilatation (FDM), NO, and adiponectin (APN) were significantly decreased while endothelin (ET-1) was significantly increased in CHD patients, while their levels were drastically changed in CHDPH patients (P<0.01). Besides, no significant differences for expression levels including FDM, APN, NO, and ET-1 was observed in CHDPH patients receiving aspirin. But the levels for FDM, APN, NO, and ET-1 were significantly changed in CHDPH patients after treatment with sildenafil for 3 months (P<0.01). The mRNA and protein levels for JNK1/2, MAPK, and NF-κB were significantly increased in CHDPH rabbits compared to the control (P<0.01), but their levels were significantly suppressed by the sildenafil application compared to the CHDPH group (P<0.01). Taken together, our study suggested that sildenafil may play a protective role on endothelial function via suppressing the JNK and NF-κB signal pathways in CHDPH patients.