K~＋通道开放剂和阻滞剂对持续缺氧大鼠肺血管收缩效应的影响

Effects of Potassium Channel Blockers and Openers on Response of Pulmonary Vasoconstriction to Sustained Hypoxia in Rats

模拟５０００ｍ高原持续缺氧引起大鼠肺动脉高压模型，研究缺氧性肺血管收缩反应（ＨＰＶ）。结果表明缺氧１０，２０ｄ大鼠肺动脉收缩压、舒张压升高。缺氧２０ｄ后，离体肺动脉灌注压（ＰＡＰＰ）和肺血管阻力（ＰＶＲ）增加。缺氧组对ＫＣｌ１０，１５ｍｍｏｌ／Ｌ引起ＰＡＰＰ和ＰＶＲ升高的反应增强。与正常组比较，缺氧２０ｄ后大鼠离体肺动脉环对ＫＣｌ１０，１５ｍｍｏｌ／Ｌ引起的收缩反应增强，对去甲肾上腺素的反应无改变。Ｋ＋通道阻滞剂ＣｓＣｌ２０ｍｍｏｌ／Ｌ可使正常大鼠肺动脉环对ＫＣｌ１０，１５ｍｍｏｌ／Ｌ引起的收缩反应加强，而缺氧大鼠则不受影响。Ｋ＋通道开放剂克罗卡林、尼可地尔可抑制ＫＣｌ引起ＰＭＰ和ＰＶＲ升高，并可抑制ＫＣｌ引起的肺动豚环收缩。提示持续缺氧会影响Ｋ＋通道，可能引起Ｋ＋通道部分阻滞，参与肺动脉高压的形成。此外，Ｋ＋通过开放剂可抑制ＨＰＶ，可能在治疗肺动脉高压中有意义。

Using potassium channel blockers and openers,the responses of pulmonary vasoconstriction were investigated in rats under the conditions of chronic hypobaric hypoxia (mimic 5000 m altitude over sea level). The systolic and distolic pulmonary artery pressure were significantly increased in rats sustained hypoxia for 10 days and 20 days. After 20 days hypoxia,the pulmonary artery perfusion pressure (PMP) and pulmonary vascular resistance ( PVR) in isolated rat lungs were 17.2±2.2 mmHg vs 13.5±2.2 mmHg in normoxia group(P<0. 01) and 1.58±0.30 mmHg. min/ml vs 1.05±0.15 mmHg,min/ml(P<0.01) respectively. And increasing PAPP and PVR by KCl 10～15 mm0l/L were also intensified in hypoxia group.The effects of KCl 10～15 mmol/L on tension of isolated pulmonary artery rings were enhanced by 20days hypoxia with the effect of norepinephrine being unchanged.The effects of potassium channel blocker CsCl 20mmol/L on increasing tension induced by KCl 10～15 mmol/Lwere enhanced in normaxia group,but not in hypoxia group.In contrast,potassium channel opener cromakalim 0.1μmol/L and nicorandil 1μmol/L reduced the increase in PAPP and PVR by KCl in both normaxia and hypoxia groups.Cromakalim and nicorandil also alleviated the increase in tension of isolated pulmonary artery rings by KCl.These results demonstrate that sustained hypoxia affects potassium channels,which is associated with formation of pulmonary hypertension.