Effects of iptakalim on the mRNA and protein expression of eNOS in pulmonary tissue of chronic hypoxic rats / 中国药理学通报

ABSTRACT

Aim To study mRNA and protein expression of eNOS in pulmonary tissue of chronic hypoxic pulmonary hypertension(HPH)rats and chronic hypoxic rats treated with novel KATP opener iptakalim.Methods sixty Sprague-Dawley(SD)male rats were randomly divided into control group, hypoxic group, low dose iptakalim group(0.75 mg·kg~(-1)·d~(-1)), and high dose iptakalim group(1.5 mg·kg~(-1)·d~(-1)).Except the first group, the other three groups were put into hypoxic and normobaric chamber (10%±0.5% O_2,8 h/day and 6 day/week) to establish chronic hypoxic model. After four weeks, the mean pulmonary arterial pressure(mPAP), RV/(LV+S)and the plasma concentration of NO were measured. RT-PCR was performed to analyze the mRNA expression of eNOS in pulmonary tissue. Western blot was performed to analyze the protein expression of eNOS, iNOS in pulmonary tissue. Results ① The level of mPAP and RV/ ( LV + S) were significantly higher in the hypoxic group than those in control group ( P < 0. 05 ) , Low dose iptakalim groupandhighdoseiptakalimgroupdecreased the level of mPAP and RV/( LV + S) significantly (P <0. 05). ② The level of NO was significantly lower in the hypoxic group than those in control group (P<0. 05). Low dose iptakalim group and high dose iptakalim group increased the level of NO significantly (P < 0. 05 ). ③ The mRNA and protein expression of eNOS in the hypoxic group were significantly lower than those in the control group (P < 0. 05 ). Low dose iptakalim group and high dose iptakalim group increased the expression of eNOS significantly ( P < 0. 05). High dose iptakalim group was more significant. Conclusion Pulmonary vascular endothelial dysfunction is induced by chronic hypoxia,and the level of NO, the mRNA and protein expression of eNOS are decreased. Iptakalim can improve the vascular endothelial dysfunction, increase the expression of eNOS and the level of NO and reverse hypoxic pulmonary hypertension.