Reeve H L, Weir E K, Nelson D P, Peterson D A, Archer S L
Minneapolis Veteran's Affairs Medical Centre, MN, USA.
Exp Physiol. 1995 Sep;80(5):825-34. doi: 10.1113/expphysiol.1995.sp003890.
K+ channels regulate tone in both the systemic and pulmonary circulations. K+ channel inhibition leads to membrane depolarization, Ca2+ influx and vasoconstriction; K+ channel activation leads to hyperpolarization and vasodilatation. The sulfhydryl oxidant diamide opens K+ channels in pulmonary smooth muscle and acts as a potent vasodilator in perfused lungs. We examined the hypothesis that antioxidants cause constriction and oxidants cause relaxation through their effects on K+ channels in vascular smooth muscle. The oxidant diamide (380 microM and 3.8 mM) inhibited the reduction of cytochrome C by ferrous sulphate in vitro whilst the antioxidants co-enzyme Q10 (770 microM) and duroquinone (700 microM) increased the rate of reduction. Both antioxidants caused dose-dependent constriction of endothelium-intact and -denuded rat pulmonary artery and aortic rings. This constriction could be reversed by 1 microM diamide. Co-enzyme Q10 and duroquinone (both at 100 microM) partially inhibited (approximately 30%) whole-cell K+ channel currents and depolarized membranes of isolated pulmonary artery smooth muscle cell recorded using the amphotericin-perforated-patch-clamp technique. Diamide (100 microM) increased whole-cell K+ channel currents and hyperpolarized the membrane. The data suggest that oxidants and antioxidants may modulate vascular tone via an effect on K+ channels.
钾离子通道调节体循环和肺循环的张力。钾离子通道抑制导致膜去极化、钙离子内流和血管收缩；钾离子通道激活导致超极化和血管舒张。巯基氧化剂二酰胺可打开肺平滑肌中的钾离子通道，并在灌注肺中作为强效血管舒张剂发挥作用。我们检验了以下假设：抗氧化剂通过影响血管平滑肌中的钾离子通道导致收缩，而氧化剂导致舒张。氧化剂二酰胺（380微摩尔和3.8毫摩尔）在体外抑制硫酸亚铁对细胞色素C的还原作用，而抗氧化剂辅酶Q10（770微摩尔）和杜醌（700微摩尔）提高了还原速率。两种抗氧化剂均引起内皮完整和去内皮的大鼠肺动脉及主动脉环的剂量依赖性收缩。这种收缩可被1微摩尔的二酰胺逆转。辅酶Q10和杜醌（均为100微摩尔）部分抑制（约30%）全细胞钾离子通道电流，并使使用两性霉素穿孔膜片钳技术记录的分离肺动脉平滑肌细胞膜去极化。二酰胺（100微摩尔）增加全细胞钾离子通道电流并使膜超极化。数据表明，氧化剂和抗氧化剂可能通过对钾离子通道的影响来调节血管张力。
