Pavord I D, Wisniewski A, Mathur R, Wahedna I, Knox A J, Tattersfield A E
Respiratory Medicine Unit, City Hospital, Nottingham.
Thorax. 1991 Sep;46(9):633-7. doi: 10.1136/thx.46.9.633.
Inhaled frusemide protects against the bronchoconstrictor response to a wide range of stimuli that cause bronchoconstriction by indirect mechanisms. One possible explanation for this protection relates to the known ability of frusemide to enhance synthesis of prostaglandin E2 (PGE2). Studies in vitro suggest that PGE2 might protect against indirectly acting bronchoconstrictor challenges rather than those that act directly on airway smooth muscle, though little is known about the effects of PGE2 in vivo. The effect of inhaled PGE2 on the bronchoconstrictor response to inhaled sodium metabisulphite (a stimulus with an indirect action) and methacholine (which acts directly on airway smooth muscle) was studied in nine patients with asthma. Subjects were studied on four days, inhaling PGE2 (100 micrograms) or placebo in a double blind fashion followed immediately by a cumulative dose challenge with sodium metabisulphite or methacholine. The response to the constrictor stimuli was measured as the provocative dose causing a 20% fall in FEV1 (PD20). There was no significant change in FEV1 after inhaled PGE2 compared with placebo, nor any significant change in the response to methacholine; the geometric mean methacholine PD20 was 0.9 mumol after PGE2 and 0.56 mumol after placebo (mean difference 0.7 (95% confidence limits--0.1, 1.5) doubling doses). PGE2, however, protected against sodium metabisulphite, the geometric mean sodium metabisulphite PD20 being 11.8 mumol after PGE2 and 1.8 mumol after placebo (mean difference 2.5 (95% CL 1.9, 3.1) doubling doses). PGE2 conferred significantly greater protection against sodium metabisulphite than methacholine (mean difference 1.8 (95% CL 0.8, 2.8) doubling doses). This suggests that PGE2, like frusemide, has an inhibitory effect on pathways relevant to the bronchoconstriction induced by sodium metabisulphite, with little or no effect on those relevant to methacholine.
吸入用速尿可预防多种通过间接机制引起支气管收缩的刺激所导致的支气管收缩反应。对此种保护作用的一种可能解释与速尿已知的增强前列腺素E2（PGE2）合成的能力有关。体外研究表明，PGE2可能预防间接作用的支气管收缩刺激，而非直接作用于气道平滑肌的刺激，尽管对PGE2在体内的作用了解甚少。在9例哮喘患者中研究了吸入PGE2对吸入偏亚硫酸氢钠（一种具有间接作用的刺激物）和乙酰甲胆碱（直接作用于气道平滑肌）引起的支气管收缩反应的影响。对受试者进行了4天的研究，以双盲方式吸入PGE2（100微克）或安慰剂，随后立即用偏亚硫酸氢钠或乙酰甲胆碱进行累积剂量激发试验。将对收缩刺激的反应测量为导致第一秒用力呼气量（FEV1）下降20%的激发剂量（PD20）。与安慰剂相比，吸入PGE2后FEV1无显著变化，对乙酰甲胆碱的反应也无显著变化；PGE2后乙酰甲胆碱PD20的几何均值为0.9微摩尔，安慰剂后为0.56微摩尔（平均差异0.7（95%置信限 -0.1，1.5）倍剂量）。然而，PGE2可预防偏亚硫酸氢钠，PGE2后偏亚硫酸氢钠PD20的几何均值为11.8微摩尔，安慰剂后为1.8微摩尔（平均差异2.5（95%置信区间1.9，3.1）倍剂量）。PGE2对偏亚硫酸氢钠的保护作用明显大于对乙酰甲胆碱的保护作用（平均差异1.8（95%置信区间0.8，2.8）倍剂量）。这表明PGE2与速尿一样，对与偏亚硫酸氢钠诱导的支气管收缩相关的途径具有抑制作用，而对与乙酰甲胆碱相关的途径几乎没有影响。
