Effects Of New K_ATP Opener Iptakalim On The MRNA Expression Of K_ATP Channels In Pulmonary Arterial Smooth Muscle Of Rats Under Chronic Hypoxia

Aim To investigate the effect of chronic hypoxia on the expression of KATP channelsubtype's mRNA in pulmonary arterial smooth muscle of rats and the effects of newKATP opener iptakalim on the mRNA expression of KATP channel subtypes inpulmonary arterial smooth muscle of rats under chronic hypoxia.Methods①Thirty male SD rats were randomly divided into three groups: thecontrol group and the two hypoxic groups consisting of simple hypoxic groups, andIPT treatment group with 10 rats each.②Rats in hypoxic group and IPT treatmentgroup were placed into anormobaric hypoxia (10%±0.5% oxygen) chamber. Rats incontrol were placed under the normal temperature and pressure with N.S treatment.③Multi-channel physiological recorder from the neck veins to right ventricle wasused to measure pulmonary arterial pressure in rats. Killed the rats and take theirhearts. Weighted the right ventricle(RV) and left ventricle and septum(LV+S),thencalculated the ratios of right ventricle/left ventricle and septum [RV/(LV+S)].④According to the American invitrogen Trizol kit's manual methods to extract thetotal RNA of the tats' smooth muscle cells.⑤Real time PCR was used to furtherdetect the expression of Kir6.1 and SUR2B mRNA in pulmonary arterial smoothmuscle of rats in the three groups.⑥Agarose gel electrophoresis was used to detectthe PCR products. ResultResults①Mean pulmonary arterial pressure(mPAP)was significantly higher inhypoxic group than those in control group and IPT group (P<0.05). There was nodifferences between the mPAP of control group and IPT group.②RV/ (LV+S) wassignificantly higher in hypoxic group than those in control group and IPTgroup(P<0.05). RV/(LV+S) had no differences between control group and IPTgroup. IPT can inhibit the pulmonary hypertension and right ventricular hypertrophyinduced by chronic hypoxia.③The mRNA expression of SUR2B was significantlylower in hypoxic group than those in control group (P<0.05) and IPT blocked theeffect of chronic hypoxia . There was no significant difference in the mRNAexpression of Kir6.1 among three groups (P>0.05).④The target genes by thetechnology of agarose gel electrophoresis was confirmed.Conclusion Chronic hypoxia can lead to the pulmonary hypertension, rightventricular hypertrophy, pulmonary remodeling and inhibit the mRNA expression ofSUR2B of KATP channels and this inhibition can be reversed by novel KATP openerIptkalim. Iptakalim had an inhibitory effect on proliferation of pulmonary arterialSMCs and had anti-remodeling properties of pulmonary artery in chronic hypoxicrats.