Effects of Pinacidil, Tetrathylammonium and Glibenclamide on Hypoxic Vasoconstriction in Isolated Perfused Rabbit Lungs / 대한마취과학회지

BACKGROUND: This study investigated the effects of the K+ channel opener, pinacidil on hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. In order to evaluate the vasodilatation mechanism of K+ channel opener, we also studied the effects of two K+ channel blocker, tetraethylammonium (TEA), a Ca2+ activated K+ channel blocker and glibenclamide (GLB), an ATP-sensitive K+ channel blocker. METHODS: Isolated lungs from white rabbits were ventilated with a normoxic gas (21%O2-5%CO2-74%N2) and a hypoxic gas (3%O2- 5%CO2-92%N2) alternatively, and then perfused with blood-containing perfusate solution. After a hypoxic pressor response (HPR) had been obtained, various drugs were added to the perfusate reservoir to achieve the predetermined circulating concentration, and the influences of the drugs on HPR were then tested. RESULTS: Pinacidil (0.3-6.0 mcM) produced a dose-dependent pulmonary vasodilation on hypoxic ventilation challenge. TEA (1 mM) caused pulmonary vasoconstriction in normoxic ventilation and potentiated a hypoxic pressor response. When the hypoxic pressor response was potentiated by TEA, pinacidil (1.0, 3.0 mcM) reduced the contraction, but GLB did not cause pulmonary vasoconstriction under normoxic ventilation, potentiate a hypoxic pressor response. CONCLUSIONS: Piacidil is capable of opposing the pulmonary responses of acute hypoxia. Moreover the effects of TEA and GLB suggest that HPV might be mediated through Ca2+ activated K+ channels, not through ATP-sensitive K+ channels.

Potassium channel blocker(4-AP)enhances the radiosensitivity of human cervical cancer cell line HeLa to ~(252)Cf neutron ray / 第三军医大学学报

Objective To investigate the potential effect of 4-amino-pynidine(4-AP)on human cervical carcinoma cell line HeLa to 252Cf neutron ray.Methods HeLa cells were treated with 4-AP(0,1,5,10,20 mmol/L,respectively)and then exposed to 0.67 Gy 252Cf neutron ray.The effect of 4-AP on proliferation of HeLa cells was assessed by MTT assay.Cell apoptosis were detected by flow cytometry.Reverse transcription polymerase chain reaction(RT-PCR)and Western blotting were used to investigate the levels of HIF-1? mRNA and protein of HeLa cells treated with 4-AP(0,20 mmol/L)and 0.67 Gy 252Cf neutron ray.Results After HeLa cells treated with 0,1,5,10,20 mmol/L 4-AP were exposed to 0.67 Gy 252Cf neutron ray for 48 h,their inhibitory rate was 0,(38.81 ?3.45)%,(46.63?3.88)%,(63.58?6.19)%,(77.51?8.87)%,and their apoptotic rate was(3.15?0.85)%,(8.01?1.19)%,(16.00?1.58)%,(47.20?3.18)%,(62.56?4.27)%,respectively,suggesting 4-AP may inhibit the proliferation of HeLa cells and induce their apoptosis in a dose-dependent manner(P0.05).However,after treated with 20 mmol/L 4-AP and exposed to 0.67 Gy 252Cf neutron ray for 24,48 and 72 h,the optical density ratio of HIF-1? mRNA/?-actin of HeLa cells was(0.401?0.121),(0.364?0.142),(0.257?0.137),(0.165?0.099),while the optical density ratio of HIF-1? protain/?-actin were(0.879?0.117),(0.645?0.115),(0.312?0.114),(0.130?0.118),showing that the levels of HIF-1? mRNA and protein both declined(P