title: Limited maximal airway narrowing in nonasthmatic subjects. Role of neural control and prostaglandin release.
abstract: In nonasthmatic subjects with normal airway responsiveness to methacholine, maximal airway narrowing is limited to a mild or moderate degree. We investigated whether the maximal response plateau or the position of the dose-response curve is due to functional inhibition by neurogenic mechanisms or to prostaglandin release. Four nonasthmatics inhaled doubling concentrations of methacholine up to 256 mg/ml (67 mg delivered during tidal breathing), followed by 4-fold-increasing doses of salbutamol up to 80 mg/ml (24 mg during tidal breathing) on 5 separate days. On each day 30 min before the test, the subjects inhaled (using a dosimeter) saline, propranolol (11 mg), or hexamethonium (910 mg) or, 2 h before the test, ingested indomethacin (75 mg) or placebo. The response to methacholine was measured from volume history standardized partial and complete maximal expiratory flow-volume curves, as FEV1 and the flows at 40% of the control FVC (V40p and V40c). Compared with saline, on average, baseline V40p was 18% lower after propranolol and 18% higher after hexamethonium. Indomethacin did not affect baseline values. There was no systematic difference between the 5 days in the dose of methacholine to cause a 10% fall in FEV1 or a 40% fall in V40p, or in the maximal response with FEV1, V40p, and V40c, or in V40p/V40c at 256 mg/ml methacholine. We conclude that limited maximal airway narrowing to methacholine in nonasthmatics is not due to a change in adrenergic, cholinergic, or ganglion-transmitted-nonadrenergic inhibitory activity nor to the release of prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: E E
authors.initials: EE
authors.lastname: Daniel
authors.forename: N
authors.initials: N
authors.lastname: Zamel
authors.forename: F E
authors.initials: FE
authors.lastname: Hargreave
mesh_terms: D000328:Adult; D000420:Albuterol; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000627:therapeutic use; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D009424:Nervous System Physiological Phenomena; D011292:Premedication; D011433:Propranolol / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D006584:Hexamethonium Compounds; D008688:Methacholine Compounds; D011453:Prostaglandins; D016210:Methacholine Chloride; D018738:Hexamethonium; D013929:Thromboxane B2; D011433:Propranolol; D000420:Albuterol; D007213:Indomethacin