title: Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit.
abstract: Nitric oxide (NO) accounts for the major effects of endothelium-derived relaxing factor. We investigated whether NO, added to the inspired gas, could exert a bronchodilatory action similar to the pulmonary vasodilation described when administering NO during lung vascular constriction. New Zealand White rabbits were intubated and mechanically-ventilated with 30% oxygen during neuroleptanaesthesia. Methacholine (MCh) was nebulized at increasing concentrations from 0.5 to 4.0 mg.ml-1, with or without inhalation of 80 parts per million (ppm) NO. The technique of rapid airway occlusion during constant-flow inflation was used for measuring respiratory mechanics, i.e. resistance and compliance of the respiratory system. Methacholine nebulization without NO inhalation raised the resistance from 51 +/- 6 (mean +/- 95% confidence interval) to 107 +/- 52 cmH2O.l-1.s at Mch 4 mg.ml-1. During NO inhalation, nebulization of MCh showed no significant increase in resistance. Arterial oxygen tension (PaO2) and compliance fell to the same extent during methacholine challenge, whether NO was inhaled or not. Closure of small airways may be a mechanism that causes the decrease in PaO2 and compliance observed. This suggests that 80 ppm NO added to the inspired gas modulates the response in central airway tone to nebulized MCh in this rabbit model. However, it appears to have less effect on peripheral airways.
authors.affiliation: Dept of Clinical Physiology, University Hospital, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Högman
authors.forename: C
authors.initials: C
authors.lastname: Frostell
authors.forename: H
authors.initials: H
authors.lastname: Arnberg
authors.forename: G
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000336:Aerosols; D016210:Methacholine Chloride; D009569:Nitric Oxide