Weir E K, Wyatt C N, Reeve H L, Huang J, Archer S L, Peers C
Department of Pharmacology, Leeds University, United Kingdom.
J Appl Physiol (1985). 1994 Jun;76(6):2611-5. doi: 10.1152/jappl.1994.76.6.2611.
Diphenyleneiodonium (DPI) blocks hypoxic vasoconstriction in the pulmonary vasculature. Because one of the actions of DPI is the inhibition of NADPH oxidase, this has led to the suggestion that NADPH oxidase acts as an oxygen tension sensor in pulmonary smooth muscle cells. We investigated the effects of DPI on potassium and calcium currents in freshly isolated pulmonary artery smooth muscle cells by using whole cell patch-clamp recordings, since these ionic currents are known to be involved in hypoxic pulmonary vasoconstriction. DPI (3 and 10 microM) reversibly inhibited potassium currents, and in its presence, residual currents appeared markedly more transient than under control conditions. The actions of DPI could not be reversed by 4.4 mM hydrogen peroxide, the product of NADPH oxidase. Calcium channel currents were also reversibly inhibited by 3 microM DPI. Thus DPI is a nonselective blocker of ionic channels in pulmonary smooth muscle cells, and its mechanism of action does not appear to involve inhibition of hydrogen peroxide formation. The ability of DPI to block calcium currents can explain its inhibition of hypoxic pulmonary vasoconstriction.
二亚苯基碘鎓（DPI）可阻断肺血管系统中的低氧性血管收缩。由于DPI的作用之一是抑制NADPH氧化酶，因此有人提出NADPH氧化酶在肺平滑肌细胞中充当氧张力传感器。我们通过全细胞膜片钳记录研究了DPI对新鲜分离的肺动脉平滑肌细胞中钾电流和钙电流的影响，因为已知这些离子电流参与低氧性肺血管收缩。DPI（3和10微摩尔）可逆地抑制钾电流，并且在其存在下，残余电流比对照条件下明显更短暂。NADPH氧化酶的产物4.4毫摩尔过氧化氢不能逆转DPI的作用。3微摩尔DPI也可逆地抑制钙通道电流。因此，DPI是肺平滑肌细胞中离子通道的非选择性阻断剂，其作用机制似乎不涉及抑制过氧化氢的形成。DPI阻断钙电流的能力可以解释其对低氧性肺血管收缩的抑制作用。
