Angiotensin-converting enzyme and the cough reflex

Lancet. 1987 Nov 14;2(8568):1116-8. doi: 10.1016/s0140-6736(87)91547-9.


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 mumol/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 mumol/l for captopril and 2.8 mumol/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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Bradykinin / metabolism
  • Captopril / pharmacology
  • Captopril / therapeutic use
  • Cough / drug therapy
  • Cough / etiology*
  • Female
  • Humans
  • Male
  • Peptidyl-Dipeptidase A / adverse effects*
  • Peptidyl-Dipeptidase A / metabolism
  • Placebos


  • Angiotensin-Converting Enzyme Inhibitors
  • Placebos
  • Captopril
  • Peptidyl-Dipeptidase A
  • Bradykinin