SB203580在电压依赖性钾离子通道阻断剂4-氨基吡啶增强大鼠低氧高二氧化碳性肺血管收缩中的作用

 目的：探索电压依赖性钾离子通道（KV）和p38 丝裂原活化蛋白激酶(MAPK)信号通路在低氧高二氧化碳性肺血管收缩（HHPV）中的作用。方法：制作正常SD大鼠离体二级肺动脉环，在常氧及低氧高二氧化碳条件下观察肺动脉环的张力变化；在急性低氧高二氧化碳条件下，分别用KV阻断剂4-氨基吡啶（4-AP）、p38 MAPK信号通路抑制剂SB203580和4-AP＋SB203580孵育二级肺动脉环，测定各组血管环的张力值。结果：在急性低氧高二氧化碳条件下，（1）肺动脉环呈现双相性的收缩(P＜0.05或P＜0.01）；（2）经4-AP孵育的二级肺动脉环，II 期收缩幅度增强（P＜005或P＜0.01）；（3）SB203580能使4-AP所致的二级肺动脉环II 期持续收缩幅度显著降低 (P＜0.05或P＜001)。结论：4-AP可增强大鼠HHPV的作用，而 SB203580能使4-AP所致的二级肺动脉环II 期持续收缩幅度显著降低，提示p38 MAPK信号通路的参与可能是KV调节大鼠HHPV作用的重要机制之一。

Role of SB203580 in enhancement of hypoxia hypercapnia-induced pulmonary vasoconstriction by voltage-dependent K+ channel blocker 4-aminopyridione in rats

AIM:To investigate the roles of voltage-dependent K+ channel (KV) and p38 mitogen-activated protein kinase (MAPK) signal pathway in the pathological process of hypoxia hypercapnia-induced pulmonary vasoconstriction (HHPV) in rats. METHODS:The second-order pulmonary artery rings isolated from SD rats in vitro was prepared, and randomly divided into control group (N group), hypoxia hypercapnia group (H group), hypoxia hypercapnia+DMSO incubation group (HD group), hypoxia hypercapnia+4-aminopyridione (4-AP) group (4-AP group), hypoxia hypercapnia+SB203580 incubation group (SB group) and hypoxia hypercapnia+4-AP+SB203580 incubation group (4-AP+SB group). Under acute hypoxia hypercapnia condition, the changes of the 3 stages of HHPV incubated by 4-AP or the combined application of 4-AP and SB203580 were observed. At the same time, the tension values of the rings were recorded. RESULTS:Under hypoxia hypercapnia condition, a biphasic pulmonary artery contractile response was observed. The phase II persistent vasoconstriction of the pulmonary artery rings incubated with 4-AP was enhanced. Under hypoxia hypercapnia condition, SB203580 significantly relieved the phase II persistent vasoconstriction induced by 4-AP. CONCLUSION: The KV blocker 4-AP enhances HHPV. SB203580 significantly relieves the phase II persistent vasoconstriction induced by 4-AP, indicating that the participation of p38 MAPK may be one of the important mechanisms for the regulation of HHPV by KV in the rats.