ATP-Sensitive Potassium Channel MRNA Expression Induced By Iptkalim In Chronic Hypoxia Pulmonary Artery Smooth Muscles Of Rats

Objective: Chronic hypoxic pulmonary hyper tension(CHPH) has been demonstrated to been the key event in the process chronic obstructive pulmonary disease (COPD) to chronic cor pulmonale, Our previous study had found that the novel ATP-sensitive potassium channel opener Iptkalim(Ipt) could prevent pulmonary hypertension in chronic hypoxic rats, so the aim of this study was to investigate if any difference exists in mRNA expression levels of ATP-sensitive potassium channe1 (KATP) in pulmonary smooth muscles between chronic hypoxic and normal rats, and to examine if any changes of KATP channel mRNA level occurred after long-term Iptkalim treated. Methods: Sprague-Dawley rats were fed in hypoxic and normobaric environment (10 ?0. 5%02, Sh-day-1 and 6 day-week-1) to establish CHPH model. Sixteen male SD rats were randomly divided into control group (NS 5ml-kg-1day-1), hypoxic group(hypoxia+NS 5ml-kg-1day-1 treated), low dose Ipt treated group(Ipt 0. 75mg-kg-1-day-1 via oral gavage +hypoxia)and high dose Ipt group (Ipt 1. 5mg-kg-1-day-1 via oral gavage +hypoxia),4 rats are included in each group. Four weeks later, the rats were executed, and the stems of pulmonary artery were immediately dissected. Reverse transcription polymerase chain reaction(RT-PCR) were performed to analyze the mRNA level of KATP channels in pulmonary main artery smooth muscles. Results: The KATP channels were expressed in pulmonary mainartery of rats. The mRNA level of SUR2 in the hypoxic group were significant lower than the control group ( 0.114 0.059 vs 0. 308 0. 031, p<0. 05 ), and high dose treated group rats had higher expression levels than the hypoxic group(0. 675 0.249 vs 0. 114 0. 059, p<0. 05), there were no difference between the other group. Kir6.1 mRNA level did not show statically significant changes across the four groups. Conclusion: The KATP transcriptional level was down-regulated in CHPH rats, and this down-regulation could be prevented by Ipt in chronic hypoxic rats. This foundings indicate that dysfunction of KATP channel may contribute to pathogenesis involved in development of pulmonary hypertension.