Elsevier

The Lancet

Volume 330, Issue 8568, 14 November 1987, Pages 1116-1118
The Lancet

ANGIOTENSIN-CONVERTING ENZYME AND THE COUGH REFLEX

https://doi.org/10.1016/S0140-6736(87)91547-9Get rights and content

Abstract

The effect of inhibition of angiotensin-converting enzyme (ACE) on standard cough challenge was investigated in a double-blind, randomised study in sixteen normal volunteers. Captopril (25 mg) or matched placebo was given by mouth 2 h before inhalation of nebulised distilled water, citric acid, and incremental doses of capsaicin (0.5-20 μmol/l). Distilled water and citric acid challenge were not significantly changed by captopril pretreatment. However, captopril significantly shifted the dose-response curve to capsaicin inhalation. The geometric mean dose of capsaicin causing 20 coughs/min was 1.3 μmol/l for captopril and 2.8 μmol/l for placebo pretreatment (p = 0.04). Cough is a recognised side-effect of ACE inhibitors; the observation that cough challenge is changed by these drugs in normal subjects implies a role for ACE in the cough reflex, possibly by metabolism of substrates other than angiotensin I.

References (30)

  • R. Lowry et al.

    Inhibition of artificially induced cough in man by bronchodilators

    Br J Clin Pharmacol

    (1987)
  • J. Collier et al.

    Capsaicin inhalation in man and the effects of sodium cromoglycate

    Br J Pharmacol

    (1984)
  • Sh Buck et al.

    The neuropharmacology of capsaicin: review of some recent observations

    Pharmacol Rev

    (1986)
  • Dj Godden et al.

    Chemical specificity of coughing in man

    Clin Sci

    (1986)
  • Cited by (217)

    • Chronic cough, a major challenge for clinicians

      2023, Revue des Maladies Respiratoires
    • Treatment of chronic cough: P2X3 receptor antagonists and beyond

      2022, Pharmacology and Therapeutics
      Citation Excerpt :

      ACE metabolises several small peptides, activating bradykinin, but metabolising SP. In 1987, this latter effect was hypothesised as the mechanism of ACE inhibitor cough due to the increased synaptic levels of SP (Morice, Brown, Lowry, & Higenbottam, 1987). The role of SP in the regulation of the cough reflex has been demonstrated centrally in the nTS, with microinjection of this neuropeptide into this region causing upregulation of cough responses. (

    • Angiotensin-Converting Enzyme Inhibitors, Asthma, and Cough: Relighting the Torch

      2021, Journal of Allergy and Clinical Immunology: In Practice
    • Quantifying test-retest variability of natural and suppressed citric acid cough thresholds and urge to cough ratings

      2019, Pulmonary Pharmacology and Therapeutics
      Citation Excerpt :

      Participants were identified by self-report to be healthy. Participants were excluded if they had a self-reported history of a neurogenic disorder; clinically significant; respiratory disease (e.g. asthma, COPD, chronic bronchitis, emphysema); gastro-esophageal reflux; taking ACE inhibitor or codeine-based drugs; were self-reported current, or previous smokers; or had a recent (<2 weeks) acute upper respiratory tract infection (URTI), as these are factors that are known to influence cough sensitivity [7,21–23]. No participants had prior experience of citric acid cough reflex testing.

    View all citing articles on Scopus
    View full text