Selective protective effects of nitric oxide inhalation on allergen-induced acute airway reactions in the pig


Roelinde J. M. Middelveld, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. E-mail:


Background Nitric oxide (NO) is thought to be an important mediator of inflammatory processes during allergic reactions in the respiratory tract.

Objective This study was undertaken to investigate the effects of inhalation of NO on the allergen-induced acute airway reactions in the pig.

Methods Specific pathogen-free pigs were sensitized with Ascaris suum antigen and challenged with an allergen aerosol during mechanical ventilation and anaesthesia. One group (n = 8) was treated with inhaled NO (20 ppm) which was given from 30 min before allergen challenge until the experiments were completed at 120 min after challenge. A control group (n = 8) did not receive NO (< 0.001 ppm).

Results Inhalation of 20 ppm NO prevented the fall in arterial pO2/FiO2 levels that was observed in the control group (areas under the curve between 0 and 120 min were 3.7 ± 1.4 kPa/min in NO-treated pigs vs. 15.9 ± 3.4 in controls, P < 0.01, Mann–Whitney U-test) and it decreased baseline pulmonary arterial pressure (change from time-point − 30–0 was 3.1 ± 5.3% in the control and − 19.9 ± 3.5% in the NO group, P < 0.01), which in turn resulted in a lower pulmonary arterial pressure during allergen challenge. NO also caused vasodilatation in the bronchial circulation, resulting in increased bronchial vascular conductance throughout the experiment. NO inhalation caused a small, but non-significant, reduction in the allergen-induced bronchoconstrictor response, whereas histamine release, as detected in urine, was not changed. Total protein levels in bronchoalveolar lavage (BAL) fluid were significantly decreased in the NO group at 120 min after challenge compared with 45 min (373 ± 101 µg/mL vs. 631 ± 184, respectively, P < 0.05, Wilcoxon matched pairs test), whereas levels in the control group did not change between these two time-points (513 ± 282 vs. 599 ± 354, not significant).

Conclusion These findings indicate that NO inhalation improves ventilation/perfusion matching and causes some bronchodilatation during the allergen-induced acute airway reaction, whereas histamine release is not affected. Moreover, NO inhalation enhanced the clearance of extravasated protein in the airways, possibly through increased bronchial blood flow. Even though some protective effects were seen, this study does not support a therapeutic role for exogenous NO in acute allergic reactions.