Angus R M, McCallum M J, Thomson N C
Department of Respiratory Medicine, Western Infirmary, Glasgow, UK.
Clin Exp Allergy. 1994 Aug;24(8):784-8. doi: 10.1111/j.1365-2222.1994.tb00991.x.
We have previously demonstrated that intravenous and inhaled atrial natriuretic peptide (ANP) significantly inhibits histamine induced bronchoconstriction in asthmatic patients. The current study was designed to determine whether inhaled ANP was also able to inhibit the effects of methacholine. Eight atopic asthmatic patients (five women) were studied: mean (SD) age 38.2 (8.3) years flow expiratory volume per second (FEV1) 2.97 (0.60) litres, equivalent to 92 (13) % of the predicted. Each had demonstrated at least mild bronchial hyperreactivity to inhaled methacholine at screening (geometric mean PC20 1.02 mg/ml; range 0.11-6.54 mg/ml). Patients attended for 3 study days and after baseline spirometry received 3.5 ml saline (placebo), 0.1 mg ANP or 1 mg ANP (ANP dissolved in 3.5 ml saline) in a randomized, double-blind manner via a Mizer aerosol conservation device. Aerosolization took approximately 9 min and FEV1 was repeated at 0.5, 1.5 and 3 min after completion. Immediately thereafter each patient received a 2 min inhalation of methacholine at a dose individually calculated to give a 25% fall in FEV1 (as extrapolated at their initial screening visit) and the FEV1 was followed over the next 20 min. Mean (SEM)% FEV1 did not change significantly after ANP being -4.3 (1.7), -3.2 (2.7) and -2.4 (1.2) after placebo, 0.1 mg ANP and 1 mg ANP respectively. The mean (SEM) maximum fall in FEV1 after methacholine was as follows: placebo 26.9 (5.7)%, 0.1 mg ANP 18.2 (4.3)% and 1.0 mg 11.2 (2.7)% (P < 0.05 placebo vs 1 mg ANP). These results demonstrate that ANP offers significant protection against methacholine induced bronchoconstriction in asthmatic patients.
我们之前已经证明，静脉注射和吸入心房利钠肽（ANP）能显著抑制组胺诱发的哮喘患者支气管收缩。本研究旨在确定吸入ANP是否也能抑制乙酰甲胆碱的作用。对8例特应性哮喘患者（5名女性）进行了研究：平均（标准差）年龄38.2（8.3）岁，一秒钟用力呼气容积（FEV1）为2.97（0.60）升，相当于预测值的92（13）%。每名患者在筛查时均至少表现出对吸入乙酰甲胆碱的轻度支气管高反应性（几何平均PC20为1.02mg/ml；范围为0.11 - 6.54mg/ml）。患者参加3个研究日，在基线肺功能测定后，通过Mizer雾化保存装置以随机、双盲方式接受3.5ml生理盐水（安慰剂）、0.1mg ANP或1mg ANP（ANP溶解于3.5ml生理盐水中）。雾化过程约9分钟，完成后在0.5、1.5和3分钟重复测量FEV1。此后，每名患者立即接受2分钟的乙酰甲胆碱吸入，剂量根据其初始筛查访视时推算，使FEV1下降25%，并在接下来的20分钟内监测FEV1。安慰剂、0.1mg ANP和1mg ANP后，平均（标准误）FEV1%变化不显著，分别为-4.3（1.7）、-3.2（2.7）和-2.4（1.2）。乙酰甲胆碱后FEV1的平均（标准误）最大下降如下：安慰剂为26.9（5.7）%，0.1mg ANP为18.2（4.3）%，1.0mg为11.2（2.7）%（安慰剂与1mg ANP相比，P < 0.05）。这些结果表明，ANP对哮喘患者乙酰甲胆碱诱发的支气管收缩具有显著的保护作用。
