一氧化碳合成酶抑制剂对缺氧性肺血管收缩反应的影响

目的 观察内皮及内源性一氧化碳（CO）合成酶抑制剂（血红素氧化酶抑制剂ZnppIX)对大鼠缺氧性肺血管收缩反应的影响，探讨内源性CO在缺氧性肺血管收缩反应中的作用。方法 制备Wistar大鼠动脉环，观察内皮与缺氧性肺血管收缩反应的关系；并以一氧化氮合成酶抑制剂L－NAME为对照，观察ZnppIX对缺氧性肺血管收缩反应的影响。结果 缺氧可使去氧肾上腺素顶收缩的肺动脉环出现明显的收缩反应，去除内皮或血管环用L－NAME孵育后，缺氧性肺血管收缩反应受抑，而用ZnppIX及L－NAME共同孵育后，缺氧性肺血管收缩反应明显抑制或消除，与L－NAME组相比有显著性差异（P＜0．01）。L－NAME组的缺氧张力变化率与未孵育前相比也有显著性差异（P＜0．01）。结论 缺氧性肺血管收缩反应是内皮依赖性的，ZnppIX可抑制大鼠氧性肺血管收缩反应，内源性CO与NO一样参与了缺氧性血管收缩反应。

Effect of carbon monoxide synthase inhibitor on hypoxic pulmonary vasoconstriction

Objective To investigate the effect of hame oxygenase inhibitor ZnppIX, an endogenous carbon monoxide (CO) synthase inhibitor, on hypoxic pulmonary vasoconstriction (HPV)of isolated rat pulmonary arterial ring (PAR), trying to explore the role of endothelium and endogenous CO in HPV.Methods Male Wistar rats (260-350g) were used. PAR (4 mm long) was prepared immediately after the animal was decapitated and suspended in Krebs-Hansleit(KH) solution maintained at 37C aerated with 5 % CO2 in O2. The arterial ring connected to a transducer-polygraph assembly for the measurement of the tension of PAR. Firstly the integrity of the endothelium of the arterial ring was tested and confirmed.In one group PAR was denuded of enothelium, then HPV of PAR was tested. PAR was preconstricted by phenylepinephrine(PE) 1μmol/L and tension was recorded as PPE . When tension reached a plateau, the KH solution was aerated with 95 % N2-5% CO2 and maintained for 30 min. The tension induced by hypoxia, was recorded as PH. The change in tension was calculated as P% . After HPV test the KH solution was washed for 30 min and the study was carried out then in two groups: L-NANE group (control group) and ZnppIX +L-NANE group. Nitric oxide synthase inhibitor, L-NANE(100 μmol/L) was added and incubated for 30 min and then HPV test was performed in control group. In ZnppIX + L-NANE group, ZnppIX(10 μmol/L)and L-NANE(100 μmol/L) were added and after 30min incubation the HPV test was conducted. The PPE, PH and P% before and after incubation and between the two groups were compared. Results Hypoxia caused vasoconstriction of PAR preconstricted by PE. Removal of endothelium or L-NANE pretreatment decreased the magnitude of constriction induced by hypoxia. However pretreatment with ZnppIX and LNANE markedly decreased or abolished the HPV as compared with control group( P<0.01 ).Conclusions HPV is endothelium dependent. ZnppIX can inhibit HPV. CO as well as NO plays an important role in HPV.