Limited maximal airway narrowing in nonasthmatic subjects. Role of neural control and prostaglandin release

Am Rev Respir Dis. 1985 Oct;132(4):865-70. doi: 10.1164/arrd.1985.132.4.865.


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)

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuterol
  • Bronchial Provocation Tests
  • Female
  • Forced Expiratory Volume
  • Hexamethonium
  • Hexamethonium Compounds / therapeutic use
  • Humans
  • Indomethacin / therapeutic use
  • Male
  • Methacholine Chloride
  • Methacholine Compounds
  • Nervous System Physiological Phenomena*
  • Premedication
  • Propranolol / therapeutic use
  • Prostaglandins / metabolism*
  • Respiratory Physiological Phenomena*
  • Thromboxane B2 / metabolism


  • Hexamethonium Compounds
  • Methacholine Compounds
  • Prostaglandins
  • Methacholine Chloride
  • Hexamethonium
  • Thromboxane B2
  • Propranolol
  • Albuterol
  • Indomethacin