慢性间歇性低压低氧对大鼠动脉血管收缩功能的影响

Effect of chronic intermittent hypobaric hypoxia on contractile activity of arteries in rats

本研究旨在探讨慢性间歇性低压低氧(chronic intermittent hypobaric hypoxia,CIHH)对大鼠胸主动脉和肺动脉收缩功能的影响及其机制。雄性Sprague-Dawley大鼠随机分为4组:CIHH处理14天组(CIHH14)、28天组(CIHH28)、42天组(CIHH42)和对照组(CON)。CIHH大鼠分别给予14、28和42天相当于海拔5000m高度、每天6h的CIHH处理;常规制备胸主动脉和肺动脉环,通过离体动脉环灌流和描记方法记录动脉的收缩活动。结果显示:(1)CIHH各组大鼠由去甲肾上腺素(noradrenaline,NA)和KCl诱发的胸主动脉和肺动脉环收缩幅度与对照大鼠无显著差异。(2)CIHH各组大鼠由血管紧张素Ⅱ(angiotensinⅡ,ANGⅡ)诱发的胸主动脉环收缩幅度较对照大鼠明显降低,而由ANGⅡ诱发的肺动脉环收缩幅度与对照大鼠无显著差异;CIHH14、28和42三组大鼠由ANGⅡ诱发的胸主动脉环收缩幅度无显著差异。(3)CIHH对ANGⅡ诱发的胸主动脉环收缩的抑制作用呈非内皮依赖性,此作用可被ATP敏感钾通道(KATP)阻断剂格列苯脲、一氧化氮合酶抑制剂L-NAME所逆转,而不被环氧合酶抑制剂吲哚美辛所阻断。结果提示,CIHH处理可非内皮依赖性地降低ANGⅡ诱发的大鼠胸主动脉收缩反应,此作用可能与KATP通道开放和NO生成增多有关。

The present study is aimed to investigate the effect of chronic intermittent hypobaric hypoxia （CIHH） on contractile activities in isolated thoracic aorta and pulmonary artery rings and the underlying mechanism in rats. Sprague-Dawley （SD） rats were randomly divided into 4 groups： control group （CON）, 14 days CIHH treatment group （CIHH14）, 28 days CIHH treatment group （CIHH28） and 42 days CIHH treatment group （CIHH42）. CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 h daily for 14, 28 and 42 d, respectively. After artery rings were prepared from pulmonary artery and thoracic aorta, the contractile activity of the artery rings was recorded using organ bath technique. Results are shown as follows. （1） There were no significant differences of noradrenaline （NA）-and KCl-induced contractions in thoracic aorta and pulmonary artery rings among CIHH and CON rats. （2） Angiotensin Ⅱ （ANGⅡ）-induced contraction in thoracic aorta rings, not in pulmonary artery rings, of CIHH rats was decreased compared with that in CON rats. There was no significant difference of ANGⅡ-induced contraction in thoracic aorta rings among CIHH rats. （3） Inhibitory effect of CIHH on ANGⅡ-induced contraction in thoracic aorta rings was endothelium-independent, and was reversed by glibenclamide （Gli）, an ATP-sensitive potassium channels （KATP） blocker, and L-NAME, a NO synthase inhibitor, but not by indomethacin （Indo）, a cyclooxygenase inhibitor. These results suggest that CIHH attenuates the contraction induced by ANGⅡ in thoracic aorta rings of rat, which is related to the opening of KATP channel and the increased production of NO.