EFFECT OF INHALED ATRIAL-NATRIURETIC-PEPTIDE ON METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN ASTHMA

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 (FEV(1)) 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 1.02mg/ml; range 0.11-6.54mg/ml). Patients attended for 3 study days and after baseline spirometry received 3.5ml saline (placebo), 0.1mg ANP or 1 mg ANP (ANP dissolved in 3.5ml saline) in a randomized, double-blind manner via a Miter aerosol conservation device. Aerosolization took approximately 9 min and FEV(1) was repeated at 0.5, 1.5 and 3 min after completion. Immediately thereafter each patient received a 2min inhalation of methacholine at a dose individually calculated to give a 25% fall in FEV(1) (as extrapolated at their initial screening visit) and the FEV(1) was followed over the next 20 min. Mean (SEM)% FEV(1) 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 FEV(1) 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.