Abstract

The effects of sildenafil on pulmonary vascular remodeling as well as potassium channels (Kv1.5) activity of pulmonary vasculature has not been clearly addressed in pulmonary hypertension secondary to left-to-right shunt. A rat model with pulmonary hypertension secondary to left-to-right shunt was established by performing an abdominal aorta to inferior vena cava fistula. Twenty-seven male Sprague-Dawley (SD) rats were randomly assigned into sham group (n = 9), shunt group (n = 9) and shunt + sildenafil group (n = 9). Rats in shunt + sildenafil group were fed with sildenafil 10 mg/kg/day instantly after shunt was established,whereas the rats in the sham group and the shunt group were fed with normal saline of the same volume. Eleven weeks later, the mean pulmonary artery pressure (mPAP), the ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV +S)], the relative medial thickness (RMT) of middle and small pulmonary muscularized arteries, as well as the expression of voltage-gated potassium channel Kv1.5 mRNA in pulmonary vasculature were detected. The rats in shunt group developed pulmonary hypertension as evidenced by significant increase in mPAP, RV/(LV +S) and RMT (all P < 0.01), meanwhile, the Kv1.5 mRNA expression in pulmonary vasculature decreased (P < 0.01). Compared with the shunt group, the rats in shunt + sildenafil group had a significant decrease in mPAP, RV/(LV+S) and RMT and a significant increase in the expression of Kv1.5 mRNA (all P < 0.01). Interestingly, there were no statistically significant differences between sham group and shunt + sildenafil group in mPAP, RV/(LV +S), RMT and expression of Kv1.5 mRNA (all P > 0.01). Sildenafil attenuates pulmonary vascular remodeling and up-regulates Kv1.5 mRNA expression in rats with pulmonary hypertension secondary to left-to-right shunt.

Key words: Sildenafil, potassium channel, pulmonary hypertension.