前列腺素、一氧化氮和钾通道在鼠兔缺氧肺血管反应钝化中的作用

Role of prostaglandins, nitric oxide and potassium channel in the blunting of hypoxic pulmonary vasoconstriction in the high altitude adaptive animal

目的 :探索前列腺素、一氧化氮和电压依赖性钾通道在高原动物鼠兔的缺氧性肺血管收缩反应钝化中的作用。方法 :用鼠兔肺组织条替代肺血管进行实验 ,并以Wistar鼠肺组织条作为对照组。分别观察环加氧酶(cyclooxygenase ,COX)抑制剂吲哚美辛 (indomethacin)、一氧化氮合酶 (nitricoxidesynthase,NOS)阻断剂L -NAME、电压门控的钾通道的阻断剂 4 -AP ,对缺氧性肺血管收缩反应的影响。结果 :(1)吲哚美辛组 :吲哚美辛使鼠兔肺组织条的缺氧张力升高平均值比用吲哚美辛前增加 6 4 7% ;Wistar鼠肺组织条仅增加 19 7% ;两组差异显著 ,P <0 0 5 ;(2 )L-NAME组 :L -NAME使鼠兔肺组织条缺氧性张力升高平均值增加 10 2 7% ;Wistar鼠肺组织条仅增加 6 0 7% ;两组差异显著 ,P <0 0 5 ;(3) 4 -AP组 :4 -AP使鼠兔肺组织条缺氧张力平均值降低 4 3 8% ;Wistar鼠肺组织条降低2 8 5 3% ;两组无显著差异 ,P >0 0 5。结论 :(1)NO和前列腺素在肺血管缺氧收缩反应中可能起调节作用 ,而电压门控的钾通道可能起介导作用 ;(2 )鼠兔肺血管对缺氧收缩反应性钝化的机制中NO和前列腺素可能起更重要的介导作用 ,而电压门控的钾通道可能不起重要作用。

AIM: To investigate the possible role of prostaglandin, NO and potassium channel in the adaptive blunting of hypoxic pulmonary vasoconstriction (HPV) in the high altitude animal (pika). METHODS: The effect of L-NAME, indomethacin and 4-AP on the response of isolated lung strips of pika and Wistar rats instead of pulmonary artery to acute hypoxia were studied. RESULTS: (1) After inhibition of prostaglandins by indomethacin, the percentage increase in hypoxic constriction in lung tissue strip of pikas was greater than that in Wistar rats[(64.7±50.9)% vs (19.7±14.1)%], P<0.05; (2) After inhibition of NO synthesis by L-NAME, the percentage increase in hypoxic constriction in lung tissue strip of pikas was greater than that in Wistar rats [(102.7±61.9)% vs (60.7±30.9)%], P<0.05; (3) After administration of 4-AP, there was no significant difference in the percentage decrease in hypoxic constriction of lung tissue strip between pika and Wistar rat. CONCLUSIONS: (1) Prostaglandins and NO might modulate HPV in the either rat pika; the closure of Voltage-gated K+ channels might mediate HPV in the either rat or pika. (2) Prostaglandins and NO might play an important role in the blunting of HPV in pika, Voltage-gated K+ channels may play a minor role in the blunting of hypoxic pulmonary vasoconstriction in pika.