慢性间歇性低压低氧对发育大鼠主动脉舒张的影响

Effect of chronic intermittent hypobaric hypoxia on relaxation of aorta and mechanisms in developing rats

目的探讨慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia,CIHH)对发育大鼠胸主动脉舒张功能的影响及作用机制。方法新生♂Sprague-Dawlay大鼠,随机分为8组:CIHH处理(CIHH)、CIHH后1周(CIHH-p1)、CIHH后2周(CIHH-p2)、CIHH后3周(CIHH-p3)、对照(Con)、1周对照(Con-1)、2周对照(Con-2)与3周对照(Con-3)。CIHH大鼠给予42 d、每天5 h、模拟海拔3 km的低压低氧处理。制备胸主动脉环,描记舒张活动。结果CIHH明显增强动脉环内皮依赖性舒张(P<0.05),此效应至少可维持3周时间(P<0.05);CIHH明显减弱急性低氧对动脉环舒张的抑制(P<0.05);CIHH对胸主动脉环舒张的增强效应及抗低氧作用可被前列环素抑制剂吲哚美辛、K ATP通道阻断剂格列本脲和氧自由基清除剂Tempo所阻断。结论CIHH处理增强发育大鼠主动脉内皮依赖性舒张,并对抗急性低氧对舒张的抑制,此作用与K ATP通道开放、前列环素和氧自由基作用有关。

Aim To investigate the effect of chronic intermittent hypobaric hypoxia(CIHH)on relaxation of thoracic aorta rings in male developing rats and the underlying mechanisms.Methods Male neonatal Sprague-Dawlay(SD)rats were randomly divided into eight groups respectively:CIHH treatment group(CIHH),group of one-week post-CIHH(CIHH-p1),group of two-week post-CIHH(CIHH-p2),group of three-week post-CIHH(CIHH-p3),control group for CIHH(Con),control group for CIHH-p1(Con-1),control group for CIHH-p2(Con-2)and control group for CIHH-p3(Con-3).Rats in CIHH groups were put into a hypobaric chamber with the mother rats 1~3 days before the birth to get a hypobaric hypoxia exposure mimicking 3 km altitude for 42 days,5 hours daily.Rats in control groups were kept in the same environment as CIHH rats except hypoxia exposure.After anaesthetized with pentobarbital sodium(50 mg·kg-1 i.p.),the thorax of rats was opened and thoracic aorta rings were made.The artery rings were placed in the bath chamber filled with K-H solution,and the relaxation of artery rings was recorded under normoxia or acute hypoxia conditions,respectively.Results(1)Under normoxia condition,the acetylcholine(ACh)-induced relaxation of thoracic aorta increased obviously in CIHH groups compared with corresponding Con groups(P<0.05).(2)The enhancing effect of CIHH treatment on thoracic aorta could be maintained for at least three weeks(P<0.05).(3)Under acute hypoxia condition,ACh-induced relaxation of thoracic aorta in each group decreased obviously,but the decrease in CIHH groups was significant less than that in Con groups(P<0.05).(4)The enhancement of CIHH on relaxation of thoracic aorta could be reversed by indomethacin(Indo),a cyclooxygenase inhibitor,glibenclamide(Gli),a K ATP blocker,and Tempo,a free radical scavenger.Conclusions CIHH augments endothelium-dependent relaxation in thoracic aorta of developing rats.Also,CIHH can antagonize the inhibition of acute hypoxia on relaxation of thoracic aorta.The enhancing effect of CIHH treatment may be related with the increase of prostacyclin,the opening of K ATP and free radical production.