Sildenafil inhibits pulmonary vascular remodeling and up-regulates voltage-gated potassium channel Kv1.5 mRNA expression in secondary pulmonary hypertension due to left-to-right shunt in rats

Abstract

Objective To investigate the effects of sildenafil on pulmonary vascular remodeling and voltage-gated potassium channeI Kv1.5 mRNA expression of pulmonary vasculature in secondary pulmonary hypertension due to left-to-right shunt in rats.Methods Male twenty-seven SD rats were randomly divided into sham group(n=9),shunt group(n=9)and shunt+sildenafil group(n=9).A left-to-right shunt was established on shunt group and shunt+sildenafil group rats by making fistula between abdominal aorta and inferior vena cava.Rats of the shunt+sildenafil group were administered sildenafil by gastric gavage at a dose of 10 mg·kg-1·d-1;whereas the rats of the sham group and the shunt group were fed with the same amount of saline. Eleven weeks later,mean pulmonary artery pressure(mPAP)and systolic pulmonary artery pressure(sPAP)were measured.The ratio of right ventricular mass to left ventricular plus septal mass[Rv/(LV+S)]was alao calculated and taken as a marker of the severity of right ventricular hypertrophy.The pathological changes of pulmonary vasculature were evaluated by calculating the relative medial thickness(RMT) of middle and small pulmonary muscularized arteries.The voltage-gated potassium channel Kv1.5 mRNA expression of pulmonary vasculature was qnantifieel using real-time PCIL Results Compared with the rats of sham grouD.the rats of shunt group had higher mPAP,sPAP,RV/(LV+S)ratio,and RMT of middie and small pulmonary muscularized(P 0.05).Conclusions Sidenafil inhibits pulmonary vascular remodeling and up-regulates Kv1.5 mRNA expression in rats with secondary pulmonary hypertension due to left-to-right shunt. Key words: Sildenafil; Kv1.5 Potassium channels; Hypertension,pulmonary